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平消胶囊抑制三阴性乳腺癌肺转移并增强乳腺癌放疗敏感性。

Pingxiao capsule inhibits lung metastasis of triple-negative breast cancer and sensitizes breast cancer to radiotherapy.

机构信息

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.

2 State Key Laboratory of Shaanxi for Natural Medicines Research and Engineering, Xi'an 710061, China.

出版信息

J Tradit Chin Med. 2023 Oct;43(5):897-905. doi: 10.19852/j.cnki.jtcm.20221121.003.

Abstract

OBJECTIVES

To investigate the anticancer effect of Pingxiao capsule (, PXC) on the treatment of breast cancer and .

METHODS

The inhibition of PXC on cell viability and proliferation was determined by cell counting kit-8, EdU assay and colony formation assay, respectively. The effect of PXC on cell apoptosis was detected by using flow cytometry. The suppression of PXC on cell migration and invasion was investigated by chamber assay. To investigate the underlying molecular mechanisms, the expression of proteins related to epithelial to mesenchymal transition (EMT) was analyzed by Western blotting in breast cancer cells and by immunohistochemistry in tumor tissues. The anticancer effect of PXC was evaluated by using MDA-MB-231 xenograft model and 4T1 metastatic breast cancer model.

RESULTS

Our results indicated that triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and MDA-MB-468 were sensitive to PXC. PXC potently inhibited the proliferation, colony formation, migration, and invasion of MDA-MB-231 and MDA-MB-468 cells . Then, MDA-MB-231 xenograft model depicted that PXC significantly reduced tumor size and weight compared with Control. 4T1 lung metastasis model showed that PXC significantly inhibited breast cancer cell spreading to lungs in mice. Mechanistically, PXC inhibited EMT process by reducing cadherin turnover in TNBC. Furthermore, PXC in combination with 8 Gy X-ray treatment obviously promoted the induction of apoptosis, and suppressed cell proliferation.

CONCLUSION

PXC could inhibit the proliferation and invasion of TNBC both and , and exerted its anti-metastatic effect by regulating cadherin turnover, Furthermore, it sensitized the TNBC cells to radiotherapy. The data supported further development of PXC as an adjuvant-therapy agent for TNBC.

摘要

目的

研究平消胶囊(PXC)在乳腺癌治疗中的抗癌作用及机制。

方法

用细胞计数试剂盒-8(CCK-8)、EdU 检测和集落形成实验分别检测 PXC 对细胞活力和增殖的抑制作用。用流式细胞术检测 PXC 对细胞凋亡的影响。用室试验研究 PXC 对细胞迁移和侵袭的抑制作用。为了研究潜在的分子机制,用 Western blot 在乳腺癌细胞中,免疫组织化学在肿瘤组织中分析与上皮间质转化(EMT)相关的蛋白表达。用 MDA-MB-231 异种移植模型和 4T1 转移性乳腺癌模型评估 PXC 的抗癌作用。

结果

我们的结果表明,三阴性乳腺癌(TNBC)细胞系 MDA-MB-231 和 MDA-MB-468 对 PXC 敏感。PXC 能强烈抑制 MDA-MB-231 和 MDA-MB-468 细胞的增殖、集落形成、迁移和侵袭。然后,MDA-MB-231 异种移植模型表明,与对照组相比,PXC 显著降低了肿瘤的大小和重量。4T1 肺转移模型表明,PXC 显著抑制了乳腺癌细胞在小鼠肺部的扩散。在机制上,PXC 通过减少 TNBC 中的钙粘蛋白周转来抑制 EMT 过程。此外,PXC 与 8 Gy X 射线治疗联合明显促进了细胞凋亡的诱导,并抑制了细胞增殖。

结论

PXC 既能抑制 TNBC 的增殖和侵袭,又能通过调节钙粘蛋白周转发挥其抗转移作用。此外,它还能使 TNBC 细胞对放疗敏感。这些数据支持进一步开发 PXC 作为 TNBC 的辅助治疗药物。

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