Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targetingEGFRandMRP2.
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 ofEGFRorMRP2increased the sensitivity to 5-FU and cisplatin in OC2 cells. Downregulation ofEGFRresulted 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 ofEGFR-downregulated cells to 5-FU. In contrast, downregulation ofMRP2was demonstrated to significantly enhance the therapeutic effects of cisplatin inEGFR-downregulated OC2 tumors. The observation that the expression ofMRP2was positively correlated with the level of cisplatin resistance in cells suggests that RNAi-mediated downregulation ofMRP2may be applicable as a therapeutic approach toward reversing MRP2-dependent cisplatin resistance in oral cancer.
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Ying-Ju
YJ
Chen
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Shiuan-Yin
SY
Chen
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Ronald
R
Lovel
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Yi-Chu
YC
Ku
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Yi-Hui
YH
Lai
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Chiao-Ling
CL
Hung
Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan, R.O.C.
Yu-Fen
YF
Li
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.; Division of Hematology-Oncology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan, R.O.C.; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan, R.O.C.
Yin-Che
YC
Lu
Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Chien-Kuo
CK
Tai
RNA interference; chemosensitivity; epidermal growth factor receptor; multidrug resistance-associated protein 2; oral cancer