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Updated: Mar 15, 2026
DNA Vector-based RNA Interference to Study Gene Function in Cancer
Published on: June 4, 2012
Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting
Ying-Ju Chen1, Shiuan-Yin Chen1, Ronald Lovel1
1Department of Life Science and Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Chia-Yi 62102, Taiwan, R.O.C.
Abstract:
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.
Insights
Targeting epidermal growth factor receptor (EGFR) or multidrug resistance-associated protein 2 (MRP2) with RNA interference enhances oral cancer cell sensitivity to chemotherapy. Downregulating EGFR improved 5-FU efficacy, while downregulating MRP2 boosted cisplatin effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Oral cancer is a significant global health concern, particularly in Taiwan.
- Chemotherapy resistance to drugs like cisplatin and 5-fluorouracil (5-FU) poses a major challenge in oral cancer treatment.
- Elevated levels of epidermal growth factor receptor (EGFR) and multidrug resistance-associated protein 2 (MRP2) are implicated in cancer drug resistance.
Purpose of the Study:
- To investigate the role of EGFR and MRP2 in chemoresistance in oral squamous cell carcinoma (OC2) cells.
- To evaluate the potential of RNA interference (RNAi) targeting EGFR and MRP2 to overcome chemotherapy resistance.
Main Methods:
- Utilized lentivirus vector-mediated RNA interference (RNAi) to downregulate EGFR and MRP2 genes in the OC2 cell line.
- Assessed the sensitivity of OC2 cells to cisplatin and 5-FU following gene downregulation.
- Evaluated the impact of EGFR and MRP2 downregulation on OC2 tumor growth in vivo.
Main Results:
- RNAi-mediated downregulation of EGFR or MRP2 significantly increased OC2 cell sensitivity to both 5-FU and cisplatin.
- EGFR downregulation suppressed OC2 tumor growth with 5-FU, but combined downregulation with MRP2 offered no additional benefit for 5-FU treatment.
- MRP2 downregulation enhanced the therapeutic efficacy of cisplatin in EGFR-downregulated tumors, suggesting a role in cisplatin resistance.
Conclusions:
- Targeting EGFR and MRP2 via RNAi can re-sensitize oral cancer cells to chemotherapy.
- Downregulating EGFR shows promise for improving 5-FU treatment outcomes.
- Downregulating MRP2 may be a viable strategy to reverse cisplatin resistance in oral cancer.
