| It is the multidrug resistance (MDR) of tumor cells to drugs that results in the failure of chemotherapy. MDR means that tumor cells can develop not only resistance to the agent employed for treatment but also cross-resistance to a spectrum of structurally and functionally diverse agents that have not been used. At present, studies show that the amplification of MDR gene and over-expression of mdrlmRNA and P-gp are the main reason that lead to MDRHepatocarcinoma is a malignant tumor with high morbidity. Although the combination of arterial infusion chemotherapy and arterial embolization technique is a good method only secondary to the excision, its long-term follow-up result is limited because of the drug resistance. In recent years, with the increasing development of interventional radiology, great progress has been made in interventional thermochemotherapy, heated saline drugs can betransferred to the focus directly by duct.The long-standing problem of hypertherima against deep tumor has been resolved by interventional thermochemotherapy, it can decline tumor's MDR and enhance the sensitivity of tumor cells to drugs. In present the mechanism of MDR have been known well, but it is little known that thermochemotherapy can affect tumor's MDR at molecular and genie level. AIM: Established efficiency and stable Vx-2mdrl cells and observe the effect of thermochemotherapy on MDR gene.Methods: I.We have established Vx-2mdrl cells with retrovirus infection by transferring plasma PHaMDRl/A to Rabbit Vx-2 cell and make it expresswhole length mdrlmRNA; 2. To study effect of hyperthermia (42.5癈 for 1 hour) x chemotherapy (ADM 32 U g/ml) and hyperthermia plus ADM on V\-2mdrl cells individually and observe the expression of mdrlmRNA and P-gp after thermochemotherapy.Results: 1. Vx-2mdrl cells line was established successfully. The cell was resistant not only to ADM but also to many other anti-tumor drugs most in use (MMC, VCR, Col),and their drug-resistant index was: 9.0> 7.9, 15.9, 21.0 times respectively; expression of P-gp on membrane and mdrlmRNA in cells were detected by immunocytochemistry and RT-PCR, the results shows that Vx-2mdrl cells expressed higher P-gp than Vx-2 cells on cell membrane, Vx-2mdrl cells expressed higher mdrlmRNA level than Vx-2 cells. 2. After hyperthermia puls ADM, a lower (or lost) expression of mdrlmRNA and lower expression of P-gp of Vx-2mdrl cells were found. Conclusions: 1. In this study we have established Vx-2mdrl cells line with retrovirus infection successfully; 2. Thermochemotherapy can decline tumor cell's expression of mdrlmRNA and P-gp, reverse tumor cell's MDR, enhance the sensitivity of tumor cells to drugs. We have studied the themochemotherapy's mechanism at molecular and genie level, which will make experimental and theoretical basis for the clinic application of interventional heated chemotherapy. |
