• Molecules and Cells
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• 제37권9호
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• pp.699-704
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• 2014

Themetastasis-associated gene 1 (MTA1) oncogene hasbeen suggested to be involved in the regulation of cancer progression. However, there is still no direct evidence that MTA1 regulates cisplatin (CDDP) resistance, as well as cancer stem cell properties. In this study, we found that MTA1 was enriched in CNE1/CDDP cells. Knock down of MTA1 in CNE1/CDDP cells reversed CSCs properties and CDDP resistance. However, ectopic expression of MTA1 in CNE1 cells induced CSCs phenotypes and CDDP insensitivity. Interestingly, ectopic overexpression of MTA1-induced CSCs properties and CDDP resistance were reversed in CNE1 cells after inhibition of PI3K/Akt by LY294002. In addition, MTA1 expression and Akt activity in CNE1/CDDP cells was much higher than that in CNE1 cells. These results suggested that MTA1 may play a critical role in promoting CDDP resistance in NPC cells by regulatingcancer stem cell properties via thePI3K/Akt signaling pathway. Our findings suggested that MTA1 may be a potential target for overcoming CDDP resistance in NPC therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4603-4606
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• 2013

Background: Cervical cancer, the second most common cancer in women, has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have antioxidant activities in vitro and in vivo. Materials and Methods: Both HeLa and SiHa cervical cancer cell lines were treated with 10% Noni, 10 mg/dl cisplatin, or a combination of both 10% Noni and 10 mg/dl cisplatin for 24 hours. Post culturing, the cells were pelleted and stored at $-70^{\circ}C$ for malondialdehyde and catalase assays. Results: On treatment with Noni, CP, and their combination, the level of MDA decreased by 0.76 fold, 0.49 fold, and 0.68 fold respectively in HeLa cells; and by 0.93 fold, 0.67 fold, and 0.79 fold respectively in SiHa cells, as compared to their controls; whereas catalase activity increased by 1.61 fold, 0.54 fold, and 2.35 fold, respectively in HeLa cells; and by 0.98 fold, 0.39 fold, and 1.85 fold respectively in SiHa cells. Conclusions: A decrease in level of lipid peroxidation and an increase in catalase activity were observed with Noni by itself and the effect ameliorated changes observed with cisplatin when given in combination.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.151-156
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• 1999

Despite the impressive antitumor activity of cisplatin, two major limitations of the drug, that is severe side effects and drug-resistance of cancer cells, make its use difficult of r cancer therapy. These limitations have resulted in a greate deal of effort having been expended into structural modifications of cisplatin. In this study, we tested two novel cisplatin analogues, (CPA)2 Pt[DOLYM] (COMP-I) and (DACH)Pt[DOLYM] (CoMP-II), for the mode of cytotoxic action against human tumor cells comparing with cisplatin and carboplatin in vitro. These two novel analogues had considerable cytotoxic activities against five kinds of human solid tumor cells, and especially COMP-II was more effective on HCT15 colon cancer cells than other compounds. In addition, COMP-II had cytostatic activity at low concentrations (10~0.3${\mu}g/ml$), but other compounds revealed little effect on tumor growth at the low concentration.

• Molecules and Cells
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• 제37권9호
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• pp.664-671
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• 2014

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.

• Molecules and Cells
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• 제42권3호
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• pp.252-261
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• 2019

The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.

• 대한한의학회지
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• 제26권2호
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• pp.1-12
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• 2005

Objectives: Malignant gliomas are often treated with cisplatin (cis-diamminedichloroplatinum(II), CDDP) and radiation but results remain unsatisfactory. Since malignant glioma displays moderate resistance to conventional therapy, a new treatment modality is needed to improve the outcome of patients with these tumors. The aim of this study was to investigate the effects of the combined use of Jongjihwan(JJH) and cisplatin(CDDP) on cultured malignant glioma cells, A172. Methodss & Results: The combined use of cisplatin and Jeongjihwan had synergistic effects on Al72 cells during 24 hr-incubation, This treatment resulted in a decrease of cell viability, Which was revealed as apoptosis Characterized by activation of caspase-3 protease as well as cleavage of poly ADP-ribose polymerase (PARP) with change of mitochondria membrane potential transition. The expression of members of the Bcl-2 protein family was modulated during co-treatment with Jeongjihwan and cisplatin. Activation of caspase-3 and mitochondrial alterations were central to co-treatment with Jeongjihwan and cisplatin-induced apoptosis. Conclusions: We conclude that co-treatment with Jeongjihwan and cisplatin-induced activation of the mitochondrial pathway enables cell death. Also, we suggest the combined theory of JJH and cisplatin could be a useful method for glioblastoma.

• 미생물과산업
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• 제33권2호
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• pp.25-26
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• 2007

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2453-2458
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• 2015

Background: X-linked inhibitor of apoptosis protein (XIAP) associated factor 1 (XAF1) exhibits aberrantly low or absent expression in various human malignancies, closely associated with anti-apoptosis and overgrowth of cancer cells. However, limited attention has been directed towards the contribution of XAF1 to invasion, apoptosis, and cisplatin (DDP)-resistance of epithelial ovarian cancer (EOC) cells. This study aimed to evaluate the potential effects of XAF1 on invasion, cell cycle, apoptosis, and cisplatin-resistance by overexpressing XAF1 in SKOV-3 and SKOV-3/DDP cells. Methods and Results: The pEGFP-C1-XAF1 plasmid was transfected into SKOV-3 and SKOV-3/DDP cells, and the expression of XAF1 at both mRNA and protein levels was analyzed by reverse transcription-PCR and Western blotting. Overexpression of XAF1 suppressed XIAP expression in both SKOV-3 and SKOV-3/DDP cells. Transwell invasion assays demonstrated that XAF1 exerted a strong anti-invasive effect in XAF1-overexpressing cells. Moreover, flow cytometry analysis revealed that XAF1 overexpression arrested the cell cycle at G0/G1 phase, and cell apoptosis analysis showed that overexpression of XAF1 enhanced apoptosis of SKOV-3 and SKOV-3/DDP cells apparently by activating caspase-9 and caspase-3. Furthermore, MTT assay confirmed a dose-dependent inhibitory effect of cisplatin in the tested tumor cells, and overexpression of XAF1 increased the sensitivity of SKOV-3 and SKOV-3/DDP cells to cisplatin-mediated antiproliferative effects. Conclusions: In summary, our data indicated that overexpression of XAF1 could suppress XIAP expression, inhibit invasion, arrest cell cycle, promote apoptosis, and confer cisplatin-sensitivity in SKOV-3 and SKOV-3/DDP cells. Therefore, XAF1 may be further assessed as a potential target for the treatment of both cisplatin-resistant and non-resistant EOCs.

• Molecules and Cells
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• 제38권5호
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• pp.396-401
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• 2015

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important redox-sensitive transcription factor that regulates the expression of several cytoprotective genes. More recently, genetic analyses of human tumors have indicated that Nrf2 may cause resistance to chemotherapy. In this study, we found that the expression levels of Nrf2 and its target genes GCLC, HO-1, NQO1 were significantly higher in cisplatin-resistant A549 (A549/CDDP) cells than those in A549 cells, and this resistance was partially reversed by Nrf2 siRNA. 3,4,5,5,7-Pentamethoxyflavone (PMF), a natural flavon extracted from Rutaceae plants, sensitized A549/CDDP to CDDP and substantially induced apoptosis compared with that of CDDP alone treated group, and this reversal effect decreased when Nrf2 was downregulated by siRNA. Mechanistically, PMF reduced Nrf2 expression leading to a reduction of Nrf2 downstream genes, and in contrast, this effect was decreased by blocking Nrf2 with siRNA. Taken together, these results demonstrated that PMF could be used as an effective adjuvant sensitizer to increase the efficacy of chemotherapeutic drugs by downregulating Nrf2 signaling pathway.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.178.1-178.1
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• 2002