| 叶建蔚,郑 超,穆艾太尔·麦提努日,毛 睿,才 层.PARP2表达对肝细胞癌模型小鼠肿瘤生长及化疗敏感性影响及其机制研究[J].现代生物医学进展英文版,2022,(19):3625-3629. |
| PARP2表达对肝细胞癌模型小鼠肿瘤生长及化疗敏感性影响及其机制研究 |
| Effects of PARP2 Expression on Tumor Growth and Chemosensitivity in Hepatocellular Carcinoma Model Mice and its Mechanism |
| Received:March 06, 2022 Revised:March 31, 2022 |
| DOI：10.13241/j.cnki.pmb.2022.19.004 |
| 中文关键词: 肝癌 PARP2 化疗 凋亡 小鼠 |
| 英文关键词: Liver cancer PARP2 Chemotherapy Apoptosis Mice |
| 基金项目:新疆维吾尔自治区自然科学基金项目（2022D01C245） |
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| 中文摘要: |
| 摘要 目的：研究聚[ADP-核糖]聚合酶2（Poly[ADP-ribose]polymerase 2, PAPR2）表达对干细胞癌模型小鼠肿瘤生长和对化疗药物敏感性的影响。方法：未转染的（对照组）、空载质粒转染（空载组）和si-PARP2转染（si-PARP2组）的Huh7细胞作为研究对象，比较体外化疗药物对不同Huh7细胞克隆形成数目和凋亡率。通过腋下皮下注射不同Huh7建立肝细胞癌模型小鼠，采用结晶紫染色观察并计数克隆形成数目；Annexin V-FITC细胞凋亡检测试剂盒检测Huh7细胞凋亡率；排水法测定肿瘤组织体积；免疫印迹法检测PARP2, B淋巴细胞瘤-2（B-cell lymphoma-2, Bcl2）和Bcl-2-Associated X蛋白（Bcl-2-Associated X, Bax）蛋白表达。结果：在体内外，转染si-PARP2均显著降低肝癌细胞中PARP2蛋白表达（P<0.05）。在体外，对照组和空载组Huh7细胞形成的细胞克隆数目和化疗药物诱导的凋亡率比较无显著差异（P>0.05）；si-PARP2组Huh7细胞形成的细胞克隆数目显著低于对照组和空载组（P<0.05），而化疗药物引起的细胞凋亡率显著高于空白组和对照组（P<0.05）。在体内，si-PARP2组小鼠肝癌移植瘤重量和体积均显著低于对照组和空载组（P<0.05）。此外，与对照组和空载组相比，肝癌移植瘤组织内细胞经阿霉素治疗后细胞凋亡率、Bax和cleaved-caspase 3蛋白表达水平显著增加（P<0.05），而Bcl2蛋白表达水平显著降低（P<0.05）。结论：PAPR2基因敲低可以显著抑制肝癌模型肿瘤生长和增强肝癌细胞对化疗药物的敏感性，其机制可能与PAPR2基因敲低促进肝癌细胞凋亡有关。 |
| 英文摘要: |
| ABSTRACT Objective: To study the effect of poly [ADP-ribose] polymerase 2 (PAPR2) expression on tumor growth and sensitivity to chemotherapeutic drugs in stem cell carcinoma model mice. Methods: Un-transfected (control group), empty plasmid-transfected (empty group) and si-PARP2-transfected (si-PARP2 group) Huh7 cells were used as the research objects, and the effect of chemotherapy drugs on the colony formation and number of different Huh7 cells in vitro was compared. Apoptosis rate. Hepatocellular carcinoma model mice were established by subcutaneous injection of different Huh7 under the armpit, and crystal violet staining was used to observe and count the number of clones formed; The apoptosis rate of Huh7 cells was detected by Annexin V-FITC apoptosis detection kit; The volume of tumor tissue was measured by the drainage method; The protein expressions of PARP2, Bax, Bcl2 and cleaved-caspase 3 were detected by western blotting. Results: In vitro and in vivo, transfection of si-PARP2 significantly decreased the expression of PARP2 protein in hepatoma cells (P<0.05). In vitro, there was no significant difference in the number of cell clones formed by Huh7 cells and the apoptosis rate induced by chemotherapy drugs between the control and empty groups(P>0.05), and the number of clones formed by Huh7 cells in the si-PARP2 group was significantly lower than that in the control and empty groups(P<0.05), while the apoptosis rate caused by chemotherapy drugs was significantly higher than that in the blank and control groups(P<0.05). In vivo, the weight and volume of hepatocellular carcinoma xenografts in the si-PARP2 group were significantly lower than those in the control and empty groups (P<0.05). In addition, compared with the control group and the empty-loaded group, the apoptosis rate, Bax and cleaved-caspase 3 protein expression levels of the cells in the hepatocellular carcinoma xenograft tissue of si-PARP2 group were significantly increased after doxorubicin treatment (P<0.05), while the Bcl2 protein expression was significantly decreased(P<0.05). Conclusion: Knockdown of PAPR2 gene can significantly inhibit tumor growth in liver cancer model and enhance the sensitivity of liver cancer cells to chemotherapeutic drugs, and the mechanism may be related to the promotion of apoptosis of liver cancer cells by knockdown of PAPR2 gene. |
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