Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2

doi:10.3892/ol.2016.4883

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標題:	Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2
作者:	Chen, Ying-Ju Chen, Shiuan-Yin Lovel, Ronald Ku, Yi-Chu Lai, Yi-Hui Hung, Chiao-Ling Li, Yu-Fen Lu, Yin-Che Tai, Chien-Kuo
貢獻者:	Natl Chung Cheng Univ, Dept Life Sci Natl Chung Cheng Univ, Inst Mol Biol & Biomed Sci China Med Univ, Inst Biostat Chiayi Christian Hosp, Div Hematol Oncol, Ditmanson Med Fdn Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr
關鍵字:	oral cancer chemosensitivity RNA interference epidermal growth factor receptor multidrug resistance-associated protein 2 abcc2
日期:	2016-09
上傳時間:	2018-01-18 11:40:13 (UTC+8)
出版者:	Spandidos Publ Ltd
摘要:	Oral cancer is the eighth most common type of cancer among men worldwide, with an age-standardized rate of 6.3 per 100,000, and is the fourth leading cause of cancer-associated mortality among men in Taiwan. Cisplatin and 5-fluorouracil (5-FU) are two of the most frequently utilized chemotherapy drugs for the treatment of oral cancer. Although oral cancer patients initially benefit from chemotherapy with these drugs, they may develop resistance to them, which worsens their prognosis and reduces survival rates. It has been reported that increased levels of epidermal growth factor receptor (EGFR) and multidrug resistance-associated protein 2 (MRP2) induce drug resistance in numerous types of human cancer. Therefore, the present study employed lentivirus vector-mediated RNA interference (RNAi) in order to target the genes encoding EGFR and MRP2 in the oral squamous cell carcinoma cell line OC2. It was observed that RNAi-mediated downregulation of EGFR or MRP2 increased the sensitivity to 5-FU and cisplatin in OC2 cells. Downregulation of EGFR resulted in significant suppression of OC2 tumor growth following 5-FU administration. However, simultaneous downregulation of the two genes did not further suppress the tumor growth, indicating that MRP2 does not have a significant role in the chemosensitivity of EGFR-downregulated cells to 5-FU. In contrast, downregulation of MRP2 was demonstrated to significantly enhance the therapeutic effects of cisplatin in EGFR-downregulated OC2 tumors. The observation that the expression of MRP2 was positively correlated with the level of cisplatin resistance in cells suggests that RNAi-mediated downregulation of MRP2 may be applicable as a therapeutic approach toward reversing MRP2-dependent cisplatin resistance in oral cancer.
關聯:	Oncology Letters, v.12 n.3, pp.2107-2114
显示于类别:	[保健營養系(所) ] 期刊論文

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