• Title/Summary/Keyword: Chemosensitivity assay

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Down-regulation of miRNA-452 is Associated with Adriamycin-resistance in Breast Cancer Cells

  • Hu, Qing;Gong, Jian-Ping;Li, Jian;Zhong, Shan-Liang;Chen, Wei-Xian;Zhang, Jun-Ying;Ma, Teng-Fei;Ji, Hao;Lv, Meng-Meng;Zhao, Jian-Hua;Tang, Jin-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5137-5142
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    • 2014
  • Adriamycin (ADR) is an important chemotherapeutic agent frequently used in treatment of breast cancer. However, resistance to ADR results in treatment failure in many patients. Recent studies have indicated that microRNAs (miRNAs) may play an important role in such drug-resistance. In the present study, microRNA-452 (miR-452) was found to be significantly down-regulated in adriamycin-resistant MCF-7 cells (MCF-7/ADR) compared with the parental MCF-7 cells by miRNA microarray and real-time quantitative PCR (RT-qPCR). MiR-452 mimics and inhibitors partially changed the adriamycin-resistance of breast cancer cells, as also confirmed by apoptosis assay. In exploring the potential mechanisms of miR-452 in the adriamycin-resistance of breast cancer cells, bioinformatics analysis, RT-qPCR and Western blotting showed that dysregulation of miR-452 played an important role in the acquired adriamycin-resistance of breast cancer, maybe at least in part via targeting insulin-like growth factor-1 receptor (IGF-1R).

AN EXPERIMENTAL STUDY ON THE RADIOSENSITIVITY AND CHEMOSENSITIVITY OF MG-63 CELL LINE (MG-63 세포주의 방사선 및 항암제감수성에 관한 실험적 연구)

  • Lee Un-Gyeong;Koh Kwang-Joon
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.26 no.2
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    • pp.121-132
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    • 1996
  • The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for human osteosarcoma MG-63 cell line using semiautomated MTT assay. 2,4, 6, 8, 10Gy were irradiated at a dose rate of 210cGy/min using /sup 60/Co Irradiator ALDORADO 8. After irradiation, MG-63 cell lines(3×10⁴ cells/ml) were exposed to bleomycin and cisplatin at concentration of 0.2, 2, 20㎍/㎖ for 1 hour respectively. The viable cells were determined for each radiation dose and/or each concentration of drug. And they were compared to control values. The obtained results were as follows : 1. There was significant difference of surviving fraction at 4, 6, 8, 10Gy on MG-63 cell line(p<0.05). 2. There was significant difference of cytotoxicity of bleomycin or cisplatin at all concentration of 0.2, 2, 20㎍/㎖ (p<0.05) on MG-63 cell line. The cytotoxicity of cisplatin was more effective than bleomycin at concentration of 20㎍/㎖ on MG-63 cell line. 3. There was significant difference of cytotoxicity of bleomycin or cisplatin at all concentration after irradiation of 2Gy on MG-63 cell line. 4. There was significant difference of cytotoxicity of bloemycin or cisplatin at concentration of 20㎍/㎖ after irradiation than that of irradiation alone(p<0.01). But there was no significant difference of cytotoxicity of bleomycin at concentration of 20㎍/㎖ after irradiation of l0Gy than that of irradiation alone.

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A STUDY ON THE RADIOSENSITIVITY AND CHEMOSENSITIVITY OF KB CELL LINE IN VITRO (시험관내 KB세포주의 방사선 및 항암제감수성에 관한 연구)

  • Hong Sung-Woo;Choi Eun-Suk;Koh Kwang-Joon
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.28 no.1
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    • pp.271-283
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    • 1998
  • The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for human squamous cell carcinoma KB cell line after radiation exposure and/or administration of antitumor drugs. 2, 4, 6, 8, 10Gy were irradiated at a dose rate of 210cGy/min using /sup 60/Co Irradiator ALDORADO 8. After irradiation, KB cell lines (3×104cells/ml) were exposed to 2㎍/ml of bleomycin or cisplatin for 1 hour. The viable cells were determined by MTT assay for each radiation dose and/or each drug at the 4th day. And they were compared to control values. The obtained results were as follows : 1. The slope of the surviving curve after irradiation of 2, 4, 6, 8, 10Gy on KB cell line was relatively steep. 2. There was no significant difference between the cytotoxicity of bleomycin compared to control group. But, there was significant difference between the cytotoxicity of cisplatin compared to control group. And the cytotoxicity of cisplatin was greater than that of bleomycin on KB cell line. 3. There were significant differences of surviving fractions after irradiation of 2Gy and 10Gy with 2㎍/ml of bleomycin compared with the groups of irradiation only on KB cell line. 4. There were significant differences of surviving fractions after irradiation of 2, 4, 6, 8, 10Gy with 2㎍/ml of cisplatin compared with the groups of irradiation only on KB cell line. 5. There was significant difference of surviving fraction between groups after irradiation of 10Gy with 2㎍/ml of bleomycin and cisplatin.

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The Effect of $I{\kappa}B{\alpha}$-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplatin and Paclitaxel ($I{\kappa}B{\alpha}$-SR 유전자이입이 Cisplatin, Paclitaxel에 대한 폐암세포주의 감수성에 미치는 영향)

  • Lee, Seok-Young;Seol, Ja-Young;Park, Kyung-Ho;Park, Gun-Min;Hwang, Yong-Il;Kim, Cheol-Hyeon;Jang, Seung-Hun;Kwon, Sung-Youn;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.2
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    • pp.122-134
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    • 2001
  • Background : Some chemotherapeutic drugs induce NF-${\kappa}B$ activation by degrading the $I{\kappa}B{\alpha}$ protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting $I{\kappa}B{\alpha}$ degradation would block NF-${\kappa}B$ activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF-${\kappa}B$ inhibitor was transferred by an adenoviral vector (Ad-$I{\kappa}B{\alpha}$-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that $I{\kappa}B{\alpha}$-SR effectively blocked the NF-${\kappa}B$ activation induced by cisplatin. Transduction with Ad-$I{\kappa}B{\alpha}$-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of $IC_{50}$. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF-${\kappa}B$ activation by inducing Ad-$I{\kappa}B{\alpha}$-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of $I{\kappa}B{\alpha}$-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

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Human Lung Cancer Cell Xenografts Implanted under the Capsule of Kidney, Spleen and Liver (폐암 세포주를 사용한 신, 비장 및 간 피막하 분식법의 비교)

  • 김수현;김종인;이해영;조봉균;박성달;김송명
    • Journal of Chest Surgery
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    • v.36 no.10
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    • pp.711-720
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    • 2003
  • Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.

Capsaicin induced apoptosis and the enhanced anticancer effect of anticancer drugs in cancer cells (종양세포에서의 capsaicin에 의한 apoptosis 유도와 항암제의 항암효과의 증가)

  • Kim, Sun Young;Lee, You Jin;Park, Eun Hye;Yi, Ho Keun;Jo, Dae Sun;Kim, Jung Soo;Hwang, Pyoung Han
    • Clinical and Experimental Pediatrics
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    • v.51 no.3
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    • pp.307-314
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    • 2008
  • Purpose : Capsaicin, the major pungent ingredient in red pepper, has long been used in spices and food additives. It has been recently shown to induce apoptosis in several cell lines through a not well known mechanism. The aim of this study was to investigate the apoptosis-inducing effect of capsaicin on gastric cancer cells, and to provide valuable information concerning the application of capsaicin for therapeutic purposes. Methods : Cultured SNU-668 cells were treated with capsaicin. We analyzed cell survival by trypan blue and crystal violet analysis, cell cytotoxicity by MTT assay, apoptosis by nuclear condensation and DNA fragmentation, bcl-2 and bax mRNA expression by RT-PCR, and the expression of apoptosis related proteins by Western immunoblot analysis. In order to assess whether the growth inhibitory effect of anticancer drugs is enhanced by capsaicin, we investigated the effects of cell cytotoxicity and the expression of apoptosis related proteins of etoposide and adriamycin treated with capsaicin in cells. Results : Capsaicin inhibited growth of SNU-668 cells in a dose-dependent manner. This inhibitory effect of capsaicin on cell growth was mainly due to the induction of apoptosis as evidenced by DNA fragmentation, nuclear condensation and the expression of apoptosis related proteins. Furthermore, capsaicin prominently reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and consequently increased caspase-3 activity. The cells treated with capsaicin were more sensitive to death induced by etoposide and adriamycin than the cells without capsaicin. Conclusion : These results demonstrate that capsaicin efficiently induced apoptosis in SNU-668 cells through a caspase-3-dependent mechanism and sensitizes cancer cells to anticancer drugs toward apoptotic cell death, which may contribute to its anticancer effect and chemosensitizer function against gastric cancer.