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Inhibitory effect of recombinant mutant human tumor necrosis factor combined with cisplatin on transplanted Lewis lung carcinoma in mice
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Abstract:
Abstract Objective: To investigate the inhibitory effect of recombinant mutant human tumor necrosis factor (rmhTNF-α) combined with cisplatin (DDP) against transplanted Lewis lung carcinoma (LLC) in mice, and to explore the related mechanism. Methods: LLC cells were subcutaneously inoculated into C57BL/6 mice at the right axilla and the mice were randomly divided into 4 groups: sodium chloride (control group),DDP group, rmhTNFα group, rmhTNFα plus DDP group. On the 7th day after inoculation the diameter of the tumor reached 0.6 cm; the corresponding agents were intratumorally injected for 3 d. All mice were sacrificed 1 d later and the tumors were obtained, weighed, and the tumor inhibitory rate was calculated. Flow cytometric analysis was used to examine cells apoptosis and cell cycle. Expression of survivin mRNA was examined by RTPCR.Results: (1)The tumor inhibitory rates of the DDP plus rmhTNFα group (3661%) was significantly higher than those of the DDP group (17.12%) and rmhTNF-α group (15.83%, P＜0.05）.The q value of Jin′s formula was 1.2, indicating a good synergistic effect between rmhTNFα and DDP. (2) The cell apoptotic rate of the rmhTNFα plus DDP group (\[28.2±1.8\]%) was significantly higher than those of the DDP group (\[21.6±1.0\]%) and rmhTNFα group (\[19.3±2.0\]%, P＜0.05）; the cells were arrested G2 phase in the DDP plus rmhTNFα group. (3) RTPCR showed that the expression of survivin gene was significantly inhibited in all the 3 groups, with the inhibition in the DDP plus rmhTNFα group more potent than that in the other 2 groups (P＜0.01). Conclusion: The combination of rmhTNFα and DDP has synergic effect in treatment of transplanted Lewis lung cancer, which might be related to the inhibition of survivin gene expression and induction of tumor cell apoptosis.
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Project Supported:
Supported by the Science and Technology Program of Heibei Province (No.072761147)
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