背景:Bazedoxifene是一种第三代选择性雌激素受体调节剂,通过抑制IL6诱导的GP130的同二聚化来抑制IL6/IL6R/GP130信号通路。考虑到IL6/IL6R/GP130信号通路在肿瘤发生和转移中的重要作用,巴多昔芬被认为具有抗肿瘤作用,已在乳腺癌和胰腺癌中得到初步证明,但尚未在非小细胞肺癌(NSCLC)中进行研究。本研究旨在评估巴泽多昔芬在NSCLC中的抗肿瘤作用。
方法:使用A549和H1299NSCLC细胞系,并暴露于各种浓度的巴多昔芬,紫杉醇,吉西他滨,以及它们对细胞活力的组合,菌落形成,和伤口愈合试验,以证明有或没有紫杉醇或吉西他滨的巴泽昔芬的抗肿瘤作用。
结果:MTT细胞活力,菌落形成,伤口愈合试验表明,巴多昔芬能够抑制细胞活力,菌落形成,和细胞以剂量依赖的方式迁移。此外,巴多昔芬能够与紫杉醇或吉西他滨协同抑制细胞活力,菌落形成,和细胞迁移。
结论:本研究证明了巴多昔芬的潜在抗肿瘤作用及其提高紫杉醇和吉西他滨治疗疗效的能力。
BACKGROUND: Bazedoxifene is a third-generation selective estrogen receptor modulator that inhibits the IL6/IL6R/GP130 signaling pathway by inhibiting IL6-induced homodimerization of GP130. Considering that the IL6/IL6R/GP130 signaling pathway is important in tumorigenesis and metastasis, bazedoxifene is thought to have an antitumor effect, which has been proven preliminarily in breast cancer and pancreatic cancer but has not yet been studied in non-small cell lung cancer (NSCLC). This study is aimed at evaluating the antitumor effect of bazedoxifene in NSCLC.
METHODS: A549 and H1299 NSCLC cell lines were employed and exposed to various concentrations of bazedoxifene, paclitaxel, gemcitabine, and their combinations for cell viability, colony formation, and wound healing assays to demonstrate the antitumor effect of bazedoxifene with or without paclitaxel or gemcitabine.
RESULTS: MTT cell viability, colony formation, and wound healing assays showed that bazedoxifene was capable of inhibiting cell viability, colony formation, and cell migration in a dose-dependent manner. In addition, bazedoxifene was capable of working with paclitaxel or gemcitabine synergistically to inhibit cell viability, colony formation, and cell migration.
CONCLUSIONS: This study demonstrated the potential antitumor effect of bazedoxifene and its ability to improve the treatment efficacy of paclitaxel and gemcitabine.