中藥QHF復(fù)方抑制乳腺癌MCF-7細(xì)胞增殖、遷移、侵襲的機(jī)制研究

Wei Hu; Dan Liu; Liang-bo Jiao; Wen Zhang; Xiang-yang Hu; Shen-tong Gan; Xin-yi Wang; Tao Chen; Wei Hu; Dan Liu; Liang-bo Jiao; Wen Zhang; Xiang-yang Hu; Shen-tong Gan; Xin-yi Wang; Tao Chen

Archive > Volume 10 Issue 4 > 2018,10(4):405-410. DOI:10.1016/j.chmed.2018.08.004 Prev Next

中藥QHF復(fù)方抑制乳腺癌MCF-7細(xì)胞增殖、遷移、侵襲的機(jī)制研究

Original articles

Mechanism of Chinese herbal formula QHF against breast cancer MCF-7 cells invasion and migration

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摘要:

摘要：目的研究中藥QHF復(fù)方對乳腺癌MCF-7細(xì)胞增殖、遷移、侵襲的影響及其可能的作用機(jī)制，為QHF的臨床應(yīng)用提供理論依據(jù)。方法體外培養(yǎng)人乳腺癌MCF-7細(xì)胞，以對數(shù)生長期的細(xì)胞為研究對象，予以不同濃度QHF復(fù)方及其他藥物，CCK8法檢測QHF復(fù)方對乳腺癌MCF-7細(xì)胞生長增殖的影響。細(xì)胞劃痕實驗和Transwell實驗檢測QHF復(fù)方對乳腺癌MCF-7細(xì)胞遷移、侵襲的影響。Western blot檢測QHF復(fù)方對乳腺癌MCF-7細(xì)胞HGF/c-Met及其下游PI3K/Akt、MAPK/ERK信號通路的影響。結(jié)果 CCK8實驗結(jié)果顯示：中藥QHF復(fù)方可不同程度抑制乳腺癌MCF-7細(xì)胞增殖且這種抑制作用可顯著拮抗HGF對乳腺癌MCF-7細(xì)胞增殖的促進(jìn)作用。細(xì)胞劃痕實驗和Transwell實驗結(jié)果顯示：中藥QHF復(fù)方能明顯抑制MCF-7細(xì)胞遷移、侵襲且這種抑制作用可拮抗HGF 對MCF-7細(xì)胞遷移、侵襲的促進(jìn)作用。Western blot實驗結(jié)果顯示：中藥QHF復(fù)方可明顯抑制乳腺癌MCF-7細(xì)胞HGF、p-c-Met、p-Akt、p-ERK、VEGF、MMP-2、MMP-9的表達(dá)。結(jié)論中藥QHF復(fù)方抑制乳腺癌MCF-7細(xì)胞的增殖、遷移和侵襲的機(jī)制可能與抑制乳腺癌MCF-7細(xì)胞異常活化的HGF/c-Met及其下游PI3K/Akt、MAPK/ERK信號通路有關(guān)。

Abstract:

Objective: To investigate the effects of Chinese herbal formula Qinghuofu (QHF) on the migration and invasion of breast cancer MCF-7 cells and its possible molecular mechanisms, thereby providing a theoretical basis to find effective anti-cancer medicine and therapeutic targets for the treatment of anti-migration and anti-invasion of breast cancer. Methods: Breast cancer MCF-7 cells were treated with different QHF and other different reagents, CCK8 assay was used to detect the influence of the reagents on the proliferation of MCF-7 cells; Scrape migration and Transwell assay were used to quantitatively determine the migration and invasion effects of QHF and HGF on the MCF-7 cells. Subsequently, the c-Met inhibitor and its downstream ERK and PI3K inhibitors were used to investigate the relationship between the migration and invasion of MCF-7 cells, as well as its downstream MAPK/ERK and PI3K/Akt signaling pathways. The expression levels of HGF, c-Met, ERK, p-Akt, p-c-Met, p-ERK, p-Akt, MMP2, MMP9, and VEGF in breast cancer MCF-7 cells treated with QHF and other reagents were also examined. Results: The result indicated that formula QHF not only significantly inhibited the proliferation of MCF-7 cells, but also significantly suppressed the effects of (hepatocyte growth factor) HGF (40 ng/mL) on the proliferation and movement of MCF-7 cells, reducing the ability of the cells to invade and migrate. Western blot analysis indicated that QHF and c-Met inhibitor significantly decreased the expression of p-c-Met, p-ERK1, p-ERK2, p-Akt, MMP-2, MMP-9, and VEGF, while HGF could significantly increase the expression of p-c-Met in MCF-7 cells; c-Met downstream ERK and PI3K inhibitors could also significantly decreased the expression of MMP-2, MMP-9, and VEGF in MCF-7 cells; But the difference among c-Met, PI3K, ERK, and QHF group were not statistically significant. Conclusion: QHF can prevent the proliferation, migration, and invasion of MCF-7 cells by inhibiting the HGF/c-Met and its downstream PI3K/Akt and MAPK/ERK signaling pathways; Thereby down-regulating the expresssion of HGF, p-Met, p-ERK1, p-ERK2, p-Akt, MMP-2, MMP-9, and VEGF.

關(guān)鍵詞:

乳腺癌;中藥QHF復(fù)方;轉(zhuǎn)移;HGF/c-Met信號通路;侵襲

Keywords:

Project Supported:

Natural Science Foundation of Hubei (no. 81573659)

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