• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6757-6760
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• 2013

Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

• Molecules and Cells
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• 제41권6호
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• pp.591-602
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• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• 대한한의학회지
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• 제25권3호
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• pp.111-122
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• 2004

Objectives : This study was carried out to investigate the effects of Jaeumgeonbi-tang extract on indomethacin-induced gastric mucosal lesions of mice. Methods : Experimental groups were classified into non-treatment group (CON group), non-administered group (GE group), misoprostol administered group (MA group) and Jaeumgeonbi-tang extract administered group (JG group). This study examined the morphological change, distribution of mast cells, mucous secreted cells and apoptotic cells, BrdU, COX-1, Hsp70, NF-κB p50, PKC, COX-2 and TNF-α of gastric mucosa. Results : 1. The hemorrhagic erosion of gastric mucosa and infiltrated mast cells were reduced in the MA and JG groups. 2. PNA reaction and mucous secreted cells were increased in the MA and JG groups. 3. The distribution of apoptotic cells, Hsp70, NF-κB p50, PKC, COX-2 and TNF-α were increased in the gastro­inflammation elicitated group, but decreased in the MA and JG groups. 4. The MA and JG groups showed increase on COX-1, BrdU. Conclusions : Jaeumgeonbi-tang extract had excellent effects on indomethacin-induced gastric mucosal lesions.

• 대한약침학회지
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• 제15권2호
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• pp.15-19
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• 2012

The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix (SR) and doxorubicin (DOX) in human gastric and colorectal adenocarcinoma cells. We used the human gastric and colorectal adenocarcinoma cell lines (MKN-45 and WIDR cells, respectively). We examined cell death by using the MTT(3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and the caspase 3 assay with SR. To examine the inhibitory effects of SR, we performed a cell cycle (sub G1) analysis for the MKN-45 and WIDR cells after three days with SR. The reversibility of SR was examined for one-day to five-day treatments with SR. SR inhibited the growth of MKN-45 and WIDR cells in a dosedependent manner. Also, we showed that SR induced apoptosis in MKN-45 and WIDR cells by using the MTT assay, the caspase 3 assay and the sub-G1 analysis. SR combined with DOX markedly inhibited the growth of MKN-45 and WIDR cells compared to SR or DOX alone. After 3 days of treating MKN-45 and WIDR cells with SR, the fraction of cells in the sub-G1 phase was much higher than that of the control group. Our findings provide insights into unraveling the effects of SR on human gastric and colorectal adenocarcinoma cells and into developing therapeutic agents for use against gastric and colorectal adenocarcinomas.

• 대한한방내과학회지
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• 제22권4호
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• pp.589-599
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• 2001

Objective: This study was carried out to investigate the effects of Hyangsayukgunja-tang extract on indomethacin-induced gastric mucosal lesions of mice. Methods: To evaluate the effects of Hyangsayukgunja-tang extract and Misoprostol, the morphology of gastric mucosa, and the distribution of mucose cells, PNA(Peanut Agglutinin), ICAM(intercellular adhesion molecule), and apoptotic cells were observed. Hyangsayukgunja-tang extract and Misoprostol were intragastric injected to the test groups at hour 72 before and just before indomethacin treatment(HYT-J, HYT-72, M-J, M-72), while the INDO group was injected only with indomethacin and the control group was subcutaneously injected only with saline. Results: The gastric mucosal lesions incresed in the fundus and body of INDO group, but softened in HYT group and M group, the effects were more excellent in the HYT-72, M-72 groups than the HYT-J, M-J groups and in the HYT group than M group. The disappearance of surface and neck mucose cells were shown in INDO group, but softened in HYT group and M group. The mucosal configuration of HYT-72 group was the same as control group. The numerical increase of PNA positive reaction in cytoplasm of perietal cells were appeared in INDO group. The PNA positive reaction in HYT group and Miso-group were shown in surface mucous cells and microvilli of apical surface in chief cells as control group, and were the same as control group in all mucosa of HYT-72 group. The distribution of ICAM positive cells, increased in INDO group, but decreased in M-72 group, and were the same as control group in HYT-72 group. The apoptotic cells, increased noticeably in gastric mucosa of INDO group, decreased in HYT group and M group, and decreased noticeably in HYT-72 group. Conclusions: Hyangsayukgunja-tang extract had excellent effects on indomethacin-induced gastric mucosal lesions.

• Journal of Gastric Cancer
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• 제3권2호
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• pp.75-79
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• 2003

Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. The Bcl-$x_{L}$/Bcl-2-associated death promoter (BAD), a member of the Bcl-2 family, is a critical regulatory component of the intrinsic cell-death pathway that exerts its pro-apoptotic effect upon heterodimerization with anti-apoptotic proteins Bcl-2 and Bcl-$X_{L}$. Expression of the BAD protein has been reported in several cancer types, but not in stomach cancer. The aim of this study was to explore the expression status of the BAD protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of the BAD protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the BAD protein in 57 ($95\%$) of the 60 cancers. Normal gastric mucosal cells showed weaker expressions of the BAD protein than gastric carcinomas. Conclusion: Taken together, these results suggest that stomach cancer cells in vivo may need BAD protein expression for apoptosis. Also, the higher expression of the BAD protein in stomach cancer cells than in normal gastric mucosal cells suggests that apoptosis might be easily triggered in susceptible stomach cancer cells, thereby producing selective pressure to make more apoptosis-resistant cells during tumor development.

• Journal of Gastric Cancer
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• 제6권3호
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• pp.132-138
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• 2006

목적: 도파민은 중추신경전달물질이지만 위장관에서 도파민수용체와 결합하여 점막상피세포 증식, 상피세포의 보호, 위암 세포증식과 관련이 있는 것으로 알려져 있다. 본 연구에서는 위암에서 기원한 세포주를 이용하여 도파민과 각각의 도파민 수용체가 위암 세포 증식과 억제에 작용하는 역할에 대해 알아보았다. 대상 및 방법: 위암세포기원에서 각각 유래한 세포주인 SNU601과 KCU-C2를 이용하여 RNA 추출 후 RT-PCR 시행 후 도파민수용체 D1, D2L과 D2S 각각에 대한 primer로 PCR을 시행하여 수용체 유전자의 상대적인 발현정도를 측정하였다. 도파민과 Dl 수용체의 대항제인 SCH 23390과 D2 수용체 대항제인 raclopride를 사용하여 약물처리에 따른 위암세포주에서 세포 증식에 대한 분석을 하였다. 결과: KCU-C2 세포주에서 D1과 D2L과 D2S 유전자 mRNA의 상대적인 발현정도는 모두 높은 발현을 보였지만, SNU 601 세포주에는 mRNA의 발현이 모두 낮은 수준이었으며, 특히 D2L mRNA는 발현되고 있지 않았다. 약물처리에 따른 위암세포주에서 세포증식에 대한 분석에서는 D1과 D2S 수용체를 통한 도파민의 신호는 세포의 증식을 억제하였고 D2L 수용체를 통한 도파민의 신호는 세포의 증식을 유도하였다. 결론: 본 연구를 통해 도파민이 위암의 세포증식과 억제에 관여하며, 도파민의 이러한 효과는 도파민의 신호가 어느 수용체를 통해 전달되었느냐에 따라 위암세포의 증식과 억제가 이루어짐을 알 수 있었다.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.370-379
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• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

• Archives of Pharmacal Research
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• 제20권5호
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• pp.410-413
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• 1997

In the course of screening synthetic compounds to inhibit tumor cell growth, pyrrolo[1,2-.alpha.] benzimidazole (PBI), an intermediate of azamitosene, was found to inhibit a proliferation of gastric cancer cell lines. Despite a potential cytotoxic activity against solid tumor cells as opposed to that against rapidly-doubled leukemic cells, there has been no report on the inhibition of gastric cancer cell line by PBI and its' derivatives. The present experiment was designed to determine if PBI derivatives can effectively inhibit the cellular proliferation of gastric cancer cells by using in vitro as well as in vivo chemosensitivity system (MTT assay, clonogenic assay and human tumor xenografted assay). Of the tested PBI derivatives, PBI (18) and PBI (20), displayed the effective growth inhibition of cultured gastric cancer cells or even in the xenografted nude mouse model.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.633-636
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• 2012

Purpose: PRIL (proliferation-inducing ligand) is a newly identified member of the tumor necrosis factor (TNF) family and modulates death ligand-induced apoptosis. Here, we investigated the effect of PRIL on cellular characteristics relating to tumor progression in human gastric cancer. Method: Recombinant lentivirus containing PRIL siRNA was constructed and then infected MGC803 and SGC7901 gastric cancer cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] colony formation and cell cycle analysis were used to study the effect of PRIL knockdown on gastric cancer cell proliferation. Results: PRIL expression in lentivirus infected cells was significantly reduced as evidenced by quantitative real-time PCR. Cell viability and colony formation of MGC803 and SGC7901 cells were significantly hampered in PRIL knock-down cells. Moreover, the cell cycle was arrested at G2/M phase, elucidating the mechanism underlying the inhibitory effect of siRNA on cell proliferation. Conclusions: Our study indicated that PRIL functions in promoting cell growth, and lentivirus-mediated PRIL gene knockdown might be a promising strategy in the treatment of gastric cancer.