EGCG对两株耐药肿瘤细胞的细胞毒增敏作用及抑瘤作用研究

目的:研究EGCG对人耐药肝癌细胞BEL7404/Adr和耐药口腔癌细胞KBV200的细胞毒增敏作用及对裸鼠移植瘤的抑瘤作用。方法:MTT法检测药物对体外培养细胞的毒性作用,采用BEL7404/ADR或KBV200细胞种植于裸鼠皮下,建立耐药肿瘤模型,观察用药后对裸鼠体重、抑瘤率、病理改变以及RTPCR和免疫组化法分别检测瘤组织mdr1和P糖蛋白的表达。结果:EGCG在100mg/L以下剂量对两株耐药肿瘤细胞的抑制率均小于10%,EGCG与抗肿瘤药物联合应用可明显提高抗肿瘤药物的细胞毒作用;体内与抗肿瘤药物联合应用对两种肿瘤抑瘤率明显高于单用抗肿瘤药物组,mdr1mRNA和Pgp的表达下降。结论:EGCG与抗肿瘤药物联合应用可增强化疗药物对耐药肿瘤细胞BEL7404/Adr和耐药口腔癌细胞KBV200的细胞毒作用,机制可能与降低MDR1mRNA表达、降低Pgp表达有关。

The study of chemotherapy sensitizing effect of EGCG on two multidrug resistant carcinoma cell lines

Objective: To study the chemotherapy sensitizing effect of EGCG on human multidrug resistant cell lines BEL-7404/ADR and KBV200 in vitro and in nude mice xenografts. Method: MTT assay was used to test the cytotoxicity of agents. MDR1 mRNA expression was detected by RT-PCR.HE staining and Immunohistochemistry was used to determine the morphology changes and expression of P-gp of xenografts of carcinoma cells. Result: The cell inhibition rate of EGCG are under 10% with the dose less than 100mg/L. In both the models of BEL -7404/Adr and KBV200 ,the inhibiting rate of the co-adminstration group increased compared with that of ADM group or VCR group each. The combination of EGCG with ADM or VCR reduced the expression of mdr1 and P-gp(P<0.01). Conclusion: EGCG combined with chemicals respectively could enhance the cytotoxicity of chemicals on BEL-7404/Adr or KBV200 in vitro and in vivo. The mechanism was possiblely related to down-regulation of the expression of mdr1 mRNA and P-glycoprotein.