参芪扶正注射液通过 PI3K 通路逆转乳腺癌 M2 巨噬细胞介导的顺铂耐药性。
Shenqi Fuzheng injection reverses M2 macrophage-mediated cisplatin resistance through the PI3K pathway in breast cancer.
机构信息
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
出版信息
PLoS One. 2023 Jan 24;18(1):e0279752. doi: 10.1371/journal.pone.0279752. eCollection 2023.
BACKGROUND
Shenqi Fuzheng injection (SQFZ) combined with chemotherapy can sensitize tumour cells. However, the mechanisms underlying SQFZ's effects remain unknown. In human breast cancer cell lines and M2 macrophages, we showed that SQFZ was a significantly potent agent of sensitization.
METHODS
The human breast cancer cell line, MDA-MB-231/DDP, and the human acute leukaemia mononuclear cell line, THP-1, were used. MDA-MB-231/DDP breast cancer xenografts were established to monitor tumour growth. Resistance-associated proteins were examined by western blotting. Levels of cytokines and chemokines were detected by ELISA. Cell viability was measured using the MTT assay. Apoptosis was detected by flow cytometric analysis.
RESULTS
SQFZ significantly enhanced the capability of cisplatin to reduce tumour mass. SQFZ and cisplatin decreased the expression of CD206 by 1.89-fold and increased that of CD86 by 1.76-fold as compared to cisplatin alone. The levels of PGE2, IL-6, and CCL1 decreased significantly, and the activation of p-PI3K and the expressions of P-gp and ABCG2 were also inhibited by SQFZ in combination with cisplatin treatment in vivo. The survival following cisplatin administration of 60 μM and 120 μM reduced significantly in the presence of SQFZ in MDA-MB-231/DDP and M2 co-cultured cells. IGF-1, a PI3K activator, combined with SQFZ weakened the effects of SQFZ-induced apoptosis from 28.7% to 10.5%. The effects of IGF-1 on increasing the expressions of P-gp, ABCG2, and Bcl-2, and decreasing that of Bax were reversed by SQFZ.
CONCLUSION
Our findings provide evidence that SQFZ is a potential therapeutic drug for cancer therapy.
背景
参芪扶正注射液（SQFZ）联合化疗可以增敏肿瘤细胞。然而，SQFZ 作用的机制尚不清楚。在人乳腺癌细胞系和 M2 巨噬细胞中，我们表明 SQFZ 是一种非常有效的增敏剂。
方法
使用人乳腺癌细胞系 MDA-MB-231/DDP 和人急性白血病单核细胞系 THP-1。建立 MDA-MB-231/DDP 乳腺癌异种移植瘤以监测肿瘤生长。通过 Western blot 检测耐药相关蛋白。通过 ELISA 检测细胞因子和趋化因子水平。通过 MTT 测定法测量细胞活力。通过流式细胞术分析检测细胞凋亡。
结果
SQFZ 显著增强了顺铂降低肿瘤质量的能力。与单独使用顺铂相比，SQFZ 和顺铂使 CD206 的表达降低了 1.89 倍，使 CD86 的表达增加了 1.76 倍。SQFZ 与顺铂联合使用可显著降低 PGE2、IL-6 和 CCL1 的水平，并抑制体内 p-PI3K 的激活以及 P-gp 和 ABCG2 的表达。在 MDA-MB-231/DDP 和 M2 共培养细胞中，当存在 SQFZ 时，顺铂给药后 60μM 和 120μM 的存活率显著降低。PI3K 激活剂 IGF-1 与 SQFZ 联合使用可将 SQFZ 诱导的凋亡率从 28.7%降至 10.5%。IGF-1 增加 P-gp、ABCG2 和 Bcl-2 的表达，降低 Bax 的表达的作用被 SQFZ 逆转。
结论
我们的研究结果提供了证据表明 SQFZ 是一种有潜力的癌症治疗药物。
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