益气除痰方增强肺癌化疗药物敏感性的作用机制

Mechanism of Yiqi Chutan formula on chemosensitivity of lung cancer

目的从内质网应激反应的角度,研究益气除痰方增强化疗药物敏感性的作用机制。方法取40只BALB/c裸鼠接种人肺腺癌细胞A549,建立裸鼠移植瘤模型,随机均分为模型组、顺铂组、益气除痰方低、高剂量组及联合用药组,造模后第8天,ig给予益气除痰方低、高剂量组及联合用药组小鼠相应剂量的益气除痰方,qd,连续14 d,第17天,ip给予顺铂组和联合用药组小鼠顺铂注射液,qd,连续5 d,第22天,检测裸鼠移植瘤的体积与瘤重,计算抑瘤率,并采用免疫组化法、RTQ-PCR法及Western blot法检测肿瘤组织中ATF6、XBP1的表达。结论益气除痰方能抑制裸鼠肺癌A549细胞的生长,与化疗药物顺铂联用能起到增效作用,其机制可能与下调内质网应激反应相关蛋白ATF6、XBP1的表达而抑制肿瘤生长有关。

OBJECTIVE To study the mechanism of Yiqi Chntan formula（YQCTF） to enhancing the chemotherapy sensitivity from endoplasmic reticulum stress - related angle. METHODS 40 nude mice models were transplanted in A549 lung cancer ceils. The mice were randomized into the model group, Cisplatin group, low dose of YQCTF group, high dose of YQCTF group and combination group. The mice of YQCTF groups and combination group were by gavaged the drugs one time a day from the 8th day after modeling for 14 consecutive days. The mice of Cisplatin group and combination group were given by intraperitoneal injection one time a day from the 17th day after modeling for 5 consecutive days. The weight ,volume and inhibitory rate of tumor were detected. The expression of ATF6 and XBP1 were detected by Immunohistochemistry,Real -time quantitative PCR and Western blotting. CONCLUSION YQCTF can inhibit A549 lung cancer cells in nude mice. Combined with chemotherapy drugs ,the killing effect on lung cancer can be enhanced. Its mechanism may be related to the down- regulated ATF6 and XBP1 of the endoplasmic reticulum stress response,were inhibiting tumor growth.