| 摘要: |
| 目的：观察黄芩苷体外对氟尿嘧啶（Fu）耐药肝癌细胞株生长的影响，并探讨其可能的作用机制。方法：体外培养人肝癌细胞BEL-7402及其耐药细胞BEL-7402/5-Fu，MTT法观察黄芩苷作用后细胞增殖情况；流式细胞术测定细胞内罗丹明123荧光强度；RT-PCR检测细胞多重耐药MDR1基因表达；Western印迹法检测细胞P-gp蛋白表达；应用Matrigel模型测定细胞黏附率；荧光免疫技术测定细胞β1-整合素（β1-integrin）和上皮钙黏附素（E-CD）蛋白表达。结果：黄芩苷明显抑制肝癌细胞BEL-7402及其耐药细胞BEL-7402/5-Fu的增殖，IC50分别为34.2、36.6 mg/L。5、10 mg/L黄芩苷能部分逆转耐药细胞对Fu的耐药，逆转倍数分别为28.6、46.7；5、10 mg/L黄芩苷增强BEL-7402对Fu敏感性，增敏倍数分别为1.4、2.1。5、10 mg/L黄芩苷增加耐药细胞内药物积聚，降低MDR1基因及P-gp蛋白表达，抑制耐药细胞黏附率，降低耐药细胞β1-整合素表达，促进E-CD蛋白表达；且10 mg/L黄芩苷效果优于5 mg/L（P均＜0.05）。结论：黄芩苷体外能抑制肝癌细胞生长及降低细胞黏附性，并能部分恢复肝癌耐药细胞对Fu的敏感性，这可能与其增加细胞内药物浓度、抑制MDR1基因表达有关。 |
| 关键词: 黄芩苷 肝肿瘤 氟尿嘧啶 抗肿瘤药耐药性 |
| DOI：10.3724/SP.J.1008.2008.00025 |
| 投稿时间：2007-10-08修订日期：2007-12-19 |
| 基金项目:河北省科技支撑计划项目（072461478D）. |
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| Inhibitory effect of baicalin on fluorouracil resistant HCC cell line BEL-7402/5-Fu and its possible mechanism |
| GUO Xia1, GUO Yu2 |
| (1.Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China;2.Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000) |
| Abstract: |
| Objective：To investigate the inhibitory effect of baicalin on the fluorouracil (Fu) resistant hepatocarcinoma cell(HCC) BEL-7402/5-Fu and its possible mechanism. Methods:Hepatocarcinoma cell line BEL-7402 and Fu-resistant hepatocarcinoma cell line BEL-7402/5-Fu were cultured in vitro. The inhibitory effect of baicalin on the BEL-7402/5-Fu cells was assessed by MTT assay; the intracellular rhodamine fluorescence intensity was observed by flow cytometry; the expression of MDR1 gene was detected by RT-PCR; and the expression of protein P-glycoprotein (P-gp) was analyzed by Western blotting assay. Adhesion assay was conducted using Matrigel model. Expression of beta 1-integrin and E-CD protein was detected by immunofluorescence technique. Results:Baicalin inhibited the proliferation of both BEL-7402 and BEL-7402/5-Fu cells, with IC50 of baicalin being 34.2 mg/L and 36.6 mg/L, respectively. Baicalin (5 mg/L and 10 mg/L) partially reversed the resistance of BEL-7402/5-Fu to Fu, with the reversal folds being 28.6 and 46.7, respectively. Baicalin (5 mg/L and 10 mg/L) increased the sensitivity of BEL-7402 cells to Fu, with the sensitivity-enhancing folds being 1.4 and 2.1, respectively. Baicalin also increased the concentration of rhodamine and expression of integrin β1, inhibited the expression of MDR1 gene and P-gp, E-CD protein, and reduced the adhesion capacity, with the effect of 10 mg/L baicalin significantly effective than that of 5 mg/L baicalin (all P＜0.05).Conclusion:Baicalin can inhibit the proliferation of BEL-7402/5-Fu in vitro, and partially reverse the resistance to Fu, which is attributable to the increased accumulation of intracellular drug concentration, inhibited expression of MDR1 gene. |
| Key words: baicalin liver neoplasm fluorouracil antineoplastic drug resistance |
