Shanghai Jiao Tong University Affiliated to Sixth People's Hospital, Shanghai, PR China.
Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, PR China.
Integr Cancer Ther. 2020 Jan-Dec;19:1534735420906463. doi: 10.1177/1534735420906463.
Chemotherapy is an effective treatment for invasive breast cancer. Paradoxically, many recently published findings showed that the first-line chemotherapeutic agent paclitaxel (PTX) showed pro-metastatic effects in the progress of treating breast cancer. Xiao-Ai-Ping (XAP) injection, composed of a traditional herbal medicine, extract, is known to exert antitumor effects on various cancers. However, there are few experimental studies on breast cancer. The underlying mechanism of the antitumor effect of XAP combined with chemotherapy agents has not been fully understood. In the present study, we sought to find the antitumor effects of XAP combined with PTX in vitro and in vivo. The data demonstrated that the combination of XAP with PTX resulted in remarkable enhancement of the pro-apoptotic, migration-inhibiting, and anti-invasive effects of PTX in vitro. Significantly, further study showed the overexpression of ATF3 in PTX-treated cell, while XAP counteracted the change of ATF3 induced by PTX. Moreover, it showed that combination treatment could promote the inhibition of tumor growth in MDA-MB-231 cell xenograft mouse model. Compared with PTX treatment, the downregulation of ATF3 indicated that ATF3 played a pivotal role in the combination of XAP with PTX to exert a synergistic effect. Overall, it is expected that PTX combined with XAP may serve as an effective agent for antitumor treatment, and dampening ATF3 maybe a potential strategy to improve the efficacy of PTX.
化疗是治疗浸润性乳腺癌的有效方法。但矛盾的是,许多最近发表的研究结果表明,一线化疗药物紫杉醇(PTX)在治疗乳腺癌的过程中表现出促转移作用。消癌平注射液是一种由传统中草药提取物组成的药物,已知对各种癌症具有抗肿瘤作用。然而,针对乳腺癌的实验研究较少,其与化疗药物联合的抗肿瘤作用机制尚未完全阐明。在本研究中,我们试图寻找消癌平联合 PTX 在体外和体内的抗肿瘤作用。结果表明,消癌平联合 PTX 可显著增强 PTX 的促凋亡、抑制迁移和抗侵袭作用。进一步的研究表明,PTX 处理的细胞中 ATF3 过表达,而消癌平可拮抗 PTX 引起的 ATF3 变化。此外,研究还表明,联合治疗可促进 MDA-MB-231 细胞异种移植小鼠模型中肿瘤生长的抑制。与 PTX 治疗相比,ATF3 的下调表明 ATF3 在消癌平联合 PTX 发挥协同作用中起着关键作用。总的来说,PTX 联合消癌平可能是一种有效的抗肿瘤治疗药物,抑制 ATF3 可能是提高 PTX 疗效的一种潜在策略。