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目的:观察果王素对肺腺癌小鼠异体移植瘤对化疗药物增敏作用,并初步探讨其作用机制。方法:构建肺腺癌小鼠移植瘤模型,将40只接种Lewis肺癌细胞的C57BL/6J小鼠随机分成5组,每组8只:正常组(生理盐水),果王素组(果王素180 mg·kg~(-1)),化疗组(顺铂联合吉西他滨),60 mg·kg~(-1)果王素联合化疗组,180 mg·kg~(-1)果王素联合化疗组;肿瘤细胞接种后4 d成瘤后给予相应药物干预,接种后20 d处死小鼠,剥离皮下肿瘤。应用Western blot法和RT-PCR检测化疗耐药相关基因切除修复交叉互补基因(ERCC1)和核糖核苷酸还原酶M1(RRM1)的表达。结果:正常组比较,各药物干预组肿瘤的生长明显受到抑制(P<0.01,P<0.05),各组抑瘤率分别为14.95%,41.77%,44.21%,59.68%。正常组ERCC1基因表达最高,各果王素药物干预组表达与正常组比较ERCC1表达明显减少,差异均有统计学意义(P<0.01),果王素组与高剂量果王素联合化疗组表达与其他各组比较明显低于其他组(P<0.01),ERCC1 mRNA表达与ERCC1蛋白表达呈一致性;正常组RRM1基因表达最高,各果王素药物干预组表达与正常组比较RRM1表达明显减少,差异均有统计学意义(P<0.01,P<0.05),果王素组与高剂量果王素联合化疗组表达与其他各组比较明显低于其他组。结论:果王素可以通过降低ERCC1表达及提高RRM1的表达增强化疗药物抑制肿瘤生长及转移的能力。
OBJECTIVE: To observe the sensitizing effects of fructus corni on chemosensitivity of allogeneic xenografted lung adenocarcinoma mice and to explore its mechanism. Methods: To construct the lung adenocarcinoma mouse xenograft model, 40 C57BL / 6J mice inoculated with Lewis lung cancer cells were randomly divided into 5 groups with 8 rats in each group: normal group (normal saline) 180 mg · kg ~ (-1)), chemotherapy group (cisplatin combined with gemcitabine), 60 mg · kg ~ (-1) The tumor cells were given tumor intervention on the 4th day after inoculation. The mice were killed 20 days after inoculation and the subcutaneous tumors were dissected. Western blot and RT-PCR were used to detect the expression of ERCC1 and RRM1 after drug resistance-related gene excision. Results: Compared with normal group, the growth of tumor in each group was significantly inhibited (P <0.01, P <0.05). The inhibition rate of each group was 14.95%, 41.77%, 44.21% and 59.68% respectively. The expression of ERCC1 in normal group was the highest, and the expression of ERCC1 in each group was significantly lower than that in normal group (P <0.01) (P <0.01). ERCC1 mRNA expression was consistent with ERCC1 protein expression in normal group. The expression of RRM1 gene in normal group was the highest, and the expression of RRM1 protein in each group was significantly lower than that in normal group , The difference was statistically significant (P <0.01, P <0.05), the combination of high-dose of fructus corni and high-dose of prometry combined with chemotherapy group was significantly lower than the other groups. CONCLUSION: Fructus puromycin can enhance the ability of chemotherapeutics to inhibit tumor growth and metastasis by decreasing ERCC1 expression and increasing RRM1 expression.