维拉帕米和α-干扰素对MCF-7/VCR癌细胞的耐药逆转作用

Reversal effect of verapamil and interferon-alpha on multidrug resistant MCF-7/VCR cells

目的探讨维拉帕米和α-干扰素(α-IFN)对于恶性肿瘤细胞的耐药逆转效果,为实体瘤供血动脉内序贯介入治疗提供实验依据。方法用6种化疗药物顺铂(DDP)、长春花碱酰胺(VDS)、5-氟尿嘧啶(5-FU)、羟基喜树碱(HCP)、丝裂霉素(MMC)、阿霉素(ADM)分别对A549肺腺癌细胞及MCF-7/VCR乳腺癌耐药细胞作药敏实验。细胞株接种前加生理盐水稀释的高浓度维拉帕米0.2mg/mL或低浓度α-IFN5U/mL,观察维拉帕米对A549细胞及MCF-7/VCR耐药细胞的细胞毒性;然后单独作MCF-7/VCR耐药细胞的维拉帕米或α-IFN逆转实验,同时加化疗药物,MTT法观察疗效。结果(1)A549细胞对DDP耐药,对其他5种药物敏感。MCF-7/VCR耐药细胞对DDP、VDS耐药,对MMC、5-FU、HCP较敏感,对ADM敏感性较低。(2)维拉帕米对A549细胞的细胞毒作用很强(抑制率98%),对MCF-7/VCR耐药细胞的抑制率80%;MCF-7/VCR耐药细胞加维拉帕米后再分别加其他化疗药物,使较敏感的药物变成敏感,使耐药的DDP增加50%敏感性,对耐药的VDS无逆转作用。(3)α-IFN和化疗药物共同作用MCF-7/VCR耐药细胞,使耐药细胞对DDP、VDS由不敏感变为较敏感,对较敏感者也有逆转作用。结论0.2mg/mL的维拉帕米或5U/mL的α-IFN对于MCF-7/VCR耐药细胞均有逆转作用,其中维拉帕米的细胞毒作用较强;维拉帕米和化疗药物共同作用MCF-7/VCR耐药细胞,对耐药的长春新碱类药物VDS无逆转作用,而α-IFN使VDS由不敏感变为较敏感,从而为实体瘤供血动脉内序贯使用不同作用机制的耐药逆转药物提供了依据。

Purpose To investigate the reversal effect of verapamil and α-interferon （α-IFN） on multidrug resistant cancer cells and to provide an experiment basis for sequential intra-artery therapy for entity tumor. Methods （1） The drug sensitivity test of A549 and MCF-7 cells which resistant to Vincristine （MCF-7/VCR） were performed with 6 kinds of chemotherapeutic drugs individually, they were DDP, VDS, 5-FU, HCP, MMC, ADM. （2） Verapamil with a high concentration of 0.2 mg/mL or α-IFN with a lower concentration of 5 U/mL was added before the cells were inoculated. The toxicity of the verapamil to A549 and MCF-7/VCR cells was observed without mixed into the chemotherapeutic drugs. Then the reversal effect of verapamil or α-IFN on drug-resistance was performed with the chemotherapeutic drugs added individually. MTT test was used to observe the effect. Results （1） A549 cells were resistant to DDP, but sensitive to another 5 kinds of drugs. MCF-7/VCR cells were resistant to DDP and VDS, relatively sensitivity to MMC, 5-FU and HCP, but lower sensitivity to ADM. （2） The toxicity of verapamil to A549 cells was very strong with an inhibitive rate 98%, but inhibitive rate to the MCF-7/VCR resistant cells was 80%. After verapamil and chemotherapeutic drug were added individually to the MCF-7/VCR cells, the relatively sensitivity drugs became sensitive and inhibitive rate of the resistant cells increased 50%, but did not reverse the resistant drug VDS. （3） After α-IFN and chemotherapeutic drugs were added individually to the MCF-7/VCR cells, the resistant drugs of DDP and VDS became relatively sensitivity, reversal effect were also shown in those drugs with lower sensitivity. Conclusions Verapamil of 0. 2 mg/mL or α-IFN of 5 U/mL had reversal effect on the MCF-7/VCR resistant cells, among them the former having a stronger cytotoxicity. Verapamil had no reversal effect on the resistant drug VDS, but α-IFN could reverse VDS from not sensitive to be more sensitive, thus provided a basis for the sequential use of different reversal modulators by intra-artery to treat the entity tumor.