| 引用本文: |
孙曦, 褚卫建, 郑易, 陆淼炯, 魏义, 尹鑫, 黄栋.6-姜烯酚对人结肠癌耐药细胞株SW620/5-Fu化疗敏感性及SDF-1α/CXCR7信号通路的影响[J].湖南中医药大学学报,2026,46(4):707-714[点击复制] |
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| 6-姜烯酚对人结肠癌耐药细胞株SW620/5-Fu化疗敏感性及SDF-1α/CXCR7信号通路的影响 |
| 孙曦,褚卫建,郑易,陆淼炯,魏义,尹鑫,黄栋 |
| (浙江中医药大学附属杭州市中医院肛肠科, 浙江 杭州 310007) |
| 摘要: |
| 目的 观察6-姜烯酚对人结肠癌耐药细胞株SW620/5-氟尿嘧啶（5-Fu）化疗敏感性的影响，并探讨其对基质细胞衍生因子-1α(SDF-1α)/CXC趋化因子受体7(CXCR7)通路的调控机制。方法 采用低剂量起始并逐步递增5-Fu浓度梯度（5、10、20、40、60、80μg/mL）的筛选策略，构建人结肠癌耐药细胞株SW620/5-Fu，随后将其分为空白组、6-姜烯酚组、5-Fu组、6-姜烯酚+5-Fu组。其中空白组加入等体积无菌生理盐水，6-姜烯酚组加入终浓度为40μmol/L的6-姜烯酚，5-Fu组加入终浓度为60μg/mL的5-Fu,6-姜烯酚+5-Fu组同时加入终浓度为40μmol/L的6-姜烯酚和60μg/mL的5-Fu。培养48 h后，倒置显微镜下观察各组细胞形态学变化；MTT法测定各组细胞增殖抑制率和药物敏感性；流式细胞术检测各组细胞凋亡率；RT-qPCR检测各组细胞SDF-1α、CXCR7、P-糖蛋白（P-gp）、B细胞淋巴瘤-2(Bcl-2)及Bcl-2相关X蛋白（Bax） mRNA表达；Western blot检测各组细胞SDF-1α、CXCR7、P-gp、Bcl-2、Bax蛋白表达水平。结果 空白组和5-Fu组细胞单层贴壁生长，为梭形或三角形，呈上皮样；6-姜烯酚组和6-姜烯酚+5-Fu组贴壁细胞明显减少，细胞缩小变圆，碎片增多，但仍呈上皮样。与空白组和5-Fu组比较，6-姜烯酚组和6-姜烯酚+5-Fu组细胞增殖抑制率、细胞凋亡率、Bax mRNA及蛋白表达水平均升高（P<0.05）；耐药指数、SDF-1α、CXCR7、P-gp、Bcl-2m RNA及蛋白表达水平均降低（P<0.05）。结论 6-姜烯酚能够抑制人结肠癌耐药细胞株SW620/5-Fu的增殖，促进其凋亡，增强其化疗敏感性，其机制可能与抑制SDF-1α/CXCR7信号通路激活，下调P-gp和Bcl-2表达，上调Bax表达有关。 |
| 关键词: 结肠癌|6-姜烯酚|化疗敏感性|基质细胞衍生因子-1α|CXC趋化因子受体7 |
| DOI：10.3969/j.issn.1674-070X.2026.04.007 |
| 投稿时间：2025-12-17 |
| 基金项目:浙江省中医药科技计划项目(2024ZL679) |
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| Effects of 6-shogaol on chemosensitivity of human colon cancer drug-resistant cell line SW620/5-Fu and the SDF-1α/CXCR7 signaling pathway |
| SUN Xi, CHU Weijian, ZHENG Yi, LU Miaojiong, WEI Yi, YIN Xin, HUANG Dong |
| (Department of Proctology, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, China) |
| Abstract: |
| Objective To observe the effects of 6-shogaol on the chemosensitivity of the human colon cancer drug-resistant cell line SW620/5-fluorouracil(5-Fu) and to explore its regulatory mechanism on the stromal cell-derived factor-1α(SDF-1α)/CXC chemokine receptor 7(CXCR7) pathway. Methods A screening strategy was employed using a gradient of 5-Fu concentrations starting at a low dose and gradually increasing(5, 10, 20, 40, 60, 80 μg/mL) to establish the human colon cancer drug-resistant cell line SW620/5-Fu. The cells were then divided into blank group, 6-shogaol group, 5-Fu group, and 6-shogaol+5-Fu group. The blank group received an equal volume of sterile normal saline. The 6-shogaol group was treated with 6-shogaol at a final concentration of40 μmol/L. The 5-Fu group was treated with 5-Fu at a final concentration of 60 μg/mL. The 6-shogaol+5-Fu group was treated with both 40 μmol/L 6-shogaol and 60 μg/mL 5-Fu. After 48 hours of culture, morphological changes of the cells in each group were observed under an inverted microscope. The cell proliferation inhibition rate and drug sensitivity were measured by MTT assay.Apoptosis rate was determined by flow cytometry. The mRNA expression levels of SDF-1α, CXCR7, P-glycoprotein(P-gp), B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax) were determined by RT-qPCR. The protein expression levels of SDF-1α,CXCR7, P-gp, Bcl-2, and Bax were examined by Western blot. Results In the blank group and the 5-Fu group, cells grew as a monolayer adherent culture, appearing spindle-or triangular-shaped with an epithelial-like morphology. In the 6-shogaol group and the 6-shogaol+5-Fu group, adherent cells were significantly reduced, cells shrank and became round, and cell debris increased,though they still exhibited an epithelial-like appearance. Compared with the blank group and the 5-Fu group, the cell proliferation inhibition rate, apoptosis rates, as well as the mRNA and protein expression levels of Bax significantly increased in the 6-shogaol group and the 6-shogaol+5-Fu group(P<0.05). Meanwhile, the drug resistance index, the mRNA and protein expression levels of SDF-1α, CXCR7, P-gp, and Bcl-2 significantly decreased(P<0.05). Conclusion 6-Shogaol can inhibit the proliferation, promote apoptosis,and enhance chemosensitivity of the human colon cancer drug-resistant cell line SW620/5-Fu. The mechanism may be associated with inhibition of the SDF-1α/CXCR7 signaling pathway, downregulation of P-gp and Bcl-2 expression, and upregulation of Bax expression. |
| Key words: colon cancer|6-shogaol|chemosensitivity|stromal cell-derived factor-1α|CXC chemokine receptor 7 |
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