| 田海燕,凌娜,高铭泽,等.硒化卡拉胶联合阿霉素对HepG-2/ADR细胞的协同抗肿瘤效应及其逆转机制研究[J].中国海洋药物,2025,(2):-. |
| 硒化卡拉胶联合阿霉素对HepG-2/ADR细胞的协同抗肿瘤效应及其逆转机制研究 |
| Synergistic antitumor effect and reversal mechanism of κ-selenocarrageenan in combination with adriamycin on HepG-2/ADR cells |
| 投稿时间：2023-12-04 修订日期：2023-12-29 |
| DOI： |
| 中文关键词: 硒化卡拉胶 阿霉素 肝癌耐药细胞HepG2 /ADM 多药耐药性 细胞凋亡 |
| English Keywords:κ-selenocarrageenan Adriamycin Hepatoma resistant cells HepG2 /ADM Multidrug resistance apoptosis |
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| 中文摘要: |
| 目的 探究硒化卡拉胶(KSC)联合阿霉素(ADR)对肝癌耐药细胞HepG-2/ADR的协同抗肿瘤效应及其逆转作用机制。方法 MTT法分别检测HepG-2/ADR耐药细胞对阿霉素、顺铂(DDP)、紫杉醇(TAX)3种化疗药物的多药耐药性,并判断KSC对HepG-2/ADR耐药细胞的逆转作用；流式细胞术检测KSC和ADR对HepG-2/ADR耐药细胞周期和细胞凋亡的影响；Western blot检测KSC和ADR对HepG-2/ADR细胞中耐药相关蛋白、细胞周期和细胞凋亡蛋白的影响。RT-qPCR进一步验证HepG-2/ADR细胞中耐药相关基因的表达。结果 MTT结果显示,HepG-2/ADR耐药细胞对ADR、TAX、DDP均具有耐药性,且KSC具有逆转肝癌HepG-2/ADR细胞多药耐药性的作用,两药联合表现为相加作用。流式细胞术表明KSC和ADR均可诱导HepG-2/ADR细胞发生凋亡和S期周期阻滞。Western blot结果显示,KSC和ADR显著下调耐药蛋白P-gp、MRP1、ABCG2以及细胞周期蛋白Cyclin A、Cyclin E、CDK2、Survivin和抑凋亡因子Bcl-2的表达(P<0.05或P<0.01),显著上调促凋亡蛋白Bax、Caspase-3、Caspase-9、Cleaved-Caspase-3和Cleaved-Caspase-9的表达(P<0.05或P<0.01)；联合组可协同促进或抑制细胞凋亡和细胞周期相关蛋白的表达。RT-qPCR表明KSC和ADR单独及联合均能显著下调P-gp1、MRP1和ABCG2耐药基因的表达。结论 KSC可有效逆转肝癌多药耐药性,协同提高HepG-2/ADR细胞对阿霉素的化疗敏感性,其机制可能与诱导细胞凋亡与细胞周期阻滞有关,通过下调多药耐药相关蛋白P-gp、MDR1和ABCG2的表达,进而逆转肝癌多药耐药性。 |
| English Summary: |
| Objective To explore the synergistic antitumor effect and reversal mechanism of κ-selenocarrageenan (KSC) in combination with adriamycin (ADR) on hepatoma resistant cell line HepG-2/ADR. Methods The multidrug resistance of HepG-2/ADR resistant cells to adriamycin (ADR), cisplatin (DDP) and paclitaxel (TAX) was detected by MTT assay, in order to evaluate the reversal effect of KSC on HepG-2/ADR cells. The effects of KSC and ADR on the cell cycle and apoptosis of HepG-2/ADR cells were detected by flow cytometry. Western blot was used to detect the expressions of drug-resistant proteins, cyclins and apoptosis-related proteins in HepG-2/ADR cells exposed to KSC and ADR. Moreover, the expressions of drug resistance related genes in HepG-2/ADR cells were further confirmed by RT-qPCR. Results MTT results displayed HepG-2/ADR cells were resistant to ADR, TAX and DDP, demonstrating multi-drug resistance. KSC could reverse the multidrug resistance of HepG-2/ADR cells, and exhibited additive effect while in combined with ADR on HepG-2/ADR cells. Flow cytometry indicated both KSC and ADR could induce apoptosis and S phase arrest of HepG-2/ADR cells. Additionally, western blot analysis showed KSC and ADR significantly downregulated the expressions of multidrug-resistant protein P-gp, MRP1 and ABCG2, as well as Cyclin A, Cyclin E, CDK2, Survivin and anti-apoptotic protein Bcl-2(P<0.05 or P<0.01), and obviously upregulated the expressions of pro-apoptotic proteins such as Bax, Caspase-3, Caspase-9, Cleaved Caspase-3, and Cleaved Caspase-9 (P<0.05 or P<0.01). Besides, the combined group could synergistically promote or inhibit the expressions of apoptosis and cell cycle-related proteins. Furthermore, RT-qPCR demonstrated KSC and ADR alone or in combination could significantly downregulate the mRNA expression of P-gp, MRP1 and ABCG2. Conclusion KSC can effectively reverse multidrug resistance of hepatoma and synergistically enhance the sensitivity of HepG-2/ADR cells to adriamycin. The mechanism may be related to the induction of apoptosis and cell cycle arrest, as well as the downregulation of P-gp, MRP1 and ABCG2 expressions, thereby reversing the multidrug resistance in liver cancer. |
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