南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (5): 904-912.doi: 10.12122/j.issn.1673-4254.2024.05.12
王媛媛(), 陈腾, 从小凡, 李依然, 陈蕊, 张配, 孙小锦(
), 赵素容(
)
收稿日期:
2023-12-20
出版日期:
2024-05-20
发布日期:
2024-06-06
通讯作者:
孙小锦,赵素容
E-mail:wangyy0424@163.com;aijosxj@163.com;inwindangel@qq.com
作者简介:
王媛媛,硕士,E-mail: wangyy0424@163.com
基金资助:
Yuanyuan WANG(), Teng CHEN, Xiaofan CONG, Yiran LI, Rui CHEN, Pei ZHANG, Xiaojin SUN(
), Surong ZHAO(
)
Received:
2023-12-20
Online:
2024-05-20
Published:
2024-06-06
Contact:
Xiaojin SUN, Surong ZHAO
E-mail:wangyy0424@163.com;aijosxj@163.com;inwindangel@qq.com
Supported by:
摘要:
目的 观察扁蒴藤素和顺铂对鼻咽癌细胞增殖和凋亡的影响,并探讨其作用机制。 方法 CCK-8法检测不同浓度扁蒴藤素、顺铂处理24 h后HNE-1和CNE-2Z细胞的存活率,集落形成实验观察细胞集落形成能力,流式细胞术检测细胞凋亡和活性氧(ROS)水平,Western blotting检测蛋白表达。N-乙酰半胱氨酸(NAC)预处理后,检测细胞增殖、凋亡及通路的影响。 结果 CCK-8结果显示,扁蒴藤素和顺铂均可抑制HNE-1和CNE-2Z细胞的存活率(P<0.05)。与单用扁蒴藤素或顺铂相比,联合使用明显抑制细胞存活率和细胞集落形成能力(P<0.05),升高细胞凋亡率(P<0.01)和细胞内ROS水平(P<0.01),上调Bax、Cleaved caspase-3和Cleaved PARP的表达(P<0.05),下调Bcl-2、Mcl-1和PARP的表达(P<0.05),同时,下调细胞中p-PI3K和p-AKT的表达(P<0.05)。而NAC可部分逆转扁蒴藤素联合顺铂对HNE-1和CNE-2Z细胞的增殖抑制(P<0.01)和凋亡诱导作用(P<0.05),部分恢复p-PI3K和p-AKT的下调作用(P<0.05)。 结论 扁蒴藤素能增强鼻咽癌细胞对顺铂的增殖抑制和凋亡诱导作用,其机制可能与ROS介导的PI3K/AKT信号通路失活有关。
王媛媛, 陈腾, 从小凡, 李依然, 陈蕊, 张配, 孙小锦, 赵素容. 扁蒴藤素通过活性氧调控PI3K/AKT通路增强顺铂诱导鼻咽癌细胞凋亡[J]. 南方医科大学学报, 2024, 44(5): 904-912.
Yuanyuan WANG, Teng CHEN, Xiaofan CONG, Yiran LI, Rui CHEN, Pei ZHANG, Xiaojin SUN, Surong ZHAO. Pristimerin enhances cisplatin-induced apoptosis in nasopharyngeal carcinoma cells via ROS-mediated deactivation of the PI3K/AKT signaling pathway[J]. Journal of Southern Medical University, 2024, 44(5): 904-912.
图1 扁蒴藤素和/或顺铂对鼻咽癌细胞活力的影响
Fig.1 Effect of pristimerin (Pri) and/or cisplatin (DDP) on viability of HNE-1 and CNE-2Z cells. A: CCK-8 assay for detecting viability of HNE-1 and CNE-2Z cells with Pri treatment. B: CCK-8 assay for detecting viability of HNE-1 and CNE-2Z cells with DDP treatment. C: CCK-8 assay for detecting viability of HNE-1 and CNE-2Z cells treated with Pri, DDP or their combination. *P<0.05, **P<0.01 vs Ctrl group, ##P<0.01.
图2 扁蒴藤素联合顺铂对鼻咽癌细胞集落形成的影响
Fig.2 Effect of Pri combined with DDP on colony formation in HNE-1 and CNE-2Z cells. *P<0.05, **P<0.01 vs Ctrl group; #P<0.05, ##P<0.01 vs Pri or DDP group.
图3 扁蒴藤素联合顺铂对鼻咽癌细胞凋亡的影响
Fig.3 Effect of Pri combined with DDP on apoptosis of HNE-1 and CNE-2Z cells. A: Apoptosis of HNE-1 and CNE-2Z cells treated with Pri and/or DDP for 24 h detected by flow cytometry. B: Expressions of Bax, Bcl-2, Mcl-1, cleaved caspase-3 and cleaved PARP in HNE-1 cells detected by Western blotting. C: Expressions of Bax, Bcl-2, Mcl-1, cleaved caspase-3 and cleaved PARP in CNE-2Z cells detected by Western blotting. *P<0.05, **P<0.01 vs Ctrl group; #P<0.05, ##P<0.01 vs Pri or DDP group.
图4 扁蒴藤素联合顺铂对鼻咽癌细胞ROS水平的影响
Fig.4 Effect of Pri combined with DDP on ROS levels in HNE-1 and CNE-2Z cells. A: ROS level of HNE-1 cells treated with Pri or DDP or their combination for 24 h detected by flow cytometry. B: ROS level in CNE-2Z cells treated with Pri or DDP or their combination for 24 h detected by flow cytometry. **P<0.01 vs Ctrl group; ##P<0.01.
图5 ROS参与扁蒴藤素联合顺铂对鼻咽癌细胞增殖和凋亡的影响
Fig.5 ROS was involved in mediating the effect of Pri combined with DDP on proliferation and apoptosis in HNE-1 and CNE-2Z cells. A: CCK-8 assay for detecting viability of HNE-1 and CNE-2Z cells treated with NAC followed by Pri combined with DDP. **P<0.01vs Ctrl group, ##P<0.01 vs Pri+DDP group. B, C: Protein levels of Bax, Bcl-2, Mcl-1, cleaved caspase-3 and cleaved PARP in HNE-1 cells and CNE-2Z cells detected by Western blotting. *P<0.05, **P<0.01 vs Pri+DDP group.
图6 扁蒴藤素联合顺铂对PI3K/AKT信号通路相关蛋白表达的影响
Fig.6 Effect of Pri combined with DDP on expression of PI3K/AKT signaling pathway-related proteins in HNE-1 and CNE-2Z cells. A, B: Protein expression levels of PI3K, AKT, p-PI3K and p-AKT in HNE-1 cells and CNE-2Z cells detected by Western blotting. *P<0.05, **P<0.01 vs Ctrl group; #P<0.05, ##P<0.01 vs Pri or DDP group. C, D: Western blotting of protein expression levels of PI3K, AKT, p-PI3K and p-AKT in HNE-1 cells and CNE-2Z cells with NAC pretreatment. *P<0.05 vs Pri+DDP group.
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