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Tetrandrine reverses the drug resistance of colon cancer to 5-fluorouracil

Kai-lei Wang, Li-na Ma, Guang-bo Bu, Gang Ma, Guang-dong Zhang, Le-ping Li, Chang-qing Jing, Cheng-kun Qin

Aim: Treatment for colon cancer is based mainly on the different stage of the cancer and chemotherapy is used as additional therapeutic approaches. 5-Fluorouracil (5-Fu) treatment is a conventional chemotherapeutical drug for colorectal cancer. However, a large amount of patients cannot be benefit from this therapy due to the resistance against 5-Fluorouracil displayed by their tumor. Tetrandrine (TET), a bisbenzylisoquinoline alkaloid, exerts antitumor effects on certain kinds of cancers. Here, we elucidate the potential application of tetrandrine to eradicate the resistance of colon cancer against 5- Fluorouracil.

Methods: Colon cancer LOVO cell line and its 5-Fu-resistanct variant, LOVO/5-Fu, were employed in this study. Those two types of cells were treated with TET for 48 hours. Afterwards, cell viability was measured by MTT colorimetric assay. Cell cycle and apoptosis were determined by flow cytometry assay. P-glycoprotein (P-gp) is believed playing a major role in the anti-drug effect of tumor cells. Thus the expression of P-gd both in mRNA and protein level were analyzed with quantitative PCR and Western blot respectively.

Results: After LOVO/5-Fu cells were treated with TET for 48h, the IC₅₀ of 5-Fu was significantly decreased to 4.15 ± 0.31 μg/ml (P<0.05); and the apoptotic rate were increased to 3.82% ± 0.12% (P<0.05). Coincidently, the expression of P-gp mRNA was significantly decreased to 570 ± 85 (P<0.05) and protein level of P-gp was also reduced respectively.

Conclusions: TET increased the sensitivity and reversed the drug-resistance of colon carcinoma cells to 5-Fu, which is relied on a P-gp-dependent manner.