CXCL8对宫颈癌细胞紫杉醇敏感性的影响及机制研究

doi:10.11904/j.issn.1002-3070.2025.01.003

实用肿瘤学杂志 ›› 2025, Vol. 39 ›› Issue (1): 13-20.doi: 10.11904/j.issn.1002-3070.2025.01.003

CXCL8对宫颈癌细胞紫杉醇敏感性的影响及机制研究

张华¹, 努尔比亚·依比布拉¹, 路鹏霏¹, 贾春丽¹, 裴轩萱², 包永星¹

1.省部共建中亚高发病成因与防治国家重点实验室,新疆医科大学第一附属医院肿瘤二科(乌鲁木齐 830000);
2.中山大学中山医学院

收稿日期:2024-08-02 修回日期:2024-12-23 出版日期:2025-02-28 发布日期:2025-03-19
通讯作者: 包永星,E-mail:baoyx@vip.sina.com
作者简介:张华,女,(1976-),博士,主任医师,从事肿瘤综合治疗的研究。
基金资助:
省部共建中亚高发病成因与防治国家重点实验室开放课题(编号:SKL-HIDCA-2020-GJ5)

Effect and mechanism of CXCL8 on the paclitaxel sensitivity of cervical cancer cells

ZHANG Hua¹, Nurbia Ibibulla¹, LU Pengfei¹, JIA Chunli¹, PEI Xuanxuan², BAO Yongxing¹

1. Department of Oncology II,The First Affiliated Hospital of Xinjiang Medical University,State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Urumqi 830000,China;
2. Zhongshan School of Medicine,Sun Yat-sen University

Received:2024-08-02 Revised:2024-12-23 Online:2025-02-28 Published:2025-03-19

摘要/Abstract

摘要： 目的探索敲低CXCL8对宫颈鳞状细胞癌紫杉醇化疗疗效的影响,并深入探究其潜在的作用机制。方法采用宫颈癌Hela细胞系,通过慢病毒介导的RNA干扰(RNAi)技术特异性地抑制CXCL8基因的表达。以HitransG P、复感染指数(multiplicity of infection,MOI)=100为最佳转染条件,CCK-8实验筛选嘌呤霉素最佳干预浓度为1.5 μg/mL;按最佳转染条件将LV-CXCL8-RNAi(3靶点)和阴性对照慢病毒转染至Hela细胞中,并设置空白对照组,qRT-PCR实验选定sh-CXCL8-13组慢病毒为后续实验的干预序列及病毒。实验分为空白对照组、阴性对照组、sh-CXCL8组、紫杉醇组以及sh-CXCL8+紫杉醇组。通过CCK-8实验和细胞侵袭实验评估Hela细胞的增殖活性及侵袭能力,利用qRT-PCR和Western blot实验检测CXCL8、Bcl2、Bax及β-actin的表达水平。结果与其余四组相比,sh-CXCL8+紫杉醇组Hela细胞活性及侵袭性显著降低,差异有统计学意义(P＜0.05)。qRT-PCR结果显示,sh-CXCL8+紫杉醇组中CXCL8、Bcl2、PIK3CB以及Akt1基因的表达量显著降低,Bax基因表达量明显上升,组间差异有统计学意义(P＜0.05)。Western blot实验结果显示,sh-CXCL8+紫杉醇组中CXCL8、PIK3CB和p-Akt1蛋白的表达量降低(P＜0.05)。结论敲低CXCL8可以降低Hela细胞增殖与侵袭能力,可能是通过影响PI3K/Akt通路来影响Hela细胞对紫杉醇的药物敏感性。

关键词: 宫颈癌, CXCL8, 紫杉醇, 敏感性, 侵袭

Abstract: Objective The Objective of this study was to explore the effect of knocking down CXCL8 on the efficacy of paclitaxel chemotherapy in cervical squamous cell carcinoma and to investigate its potential mechanism of action. Methods The Hela cell model was used to specifically inhibit CXCL8 gene expression through lentivirus-mediated RNA interference(RNAi)technology.The optimal transfection conditions were HitransG P and a multiplicity of infection(MOI)of 100.The CCK-8 assay was used to screen the optimal intervention concentration of puromycin as 1.5 μg/mL.The LV-CXCL8-RNAi(3 targets)and negative control lentivirus were transfected into cells under optimal transfection conditions and set up a blank control group.The qRT-PCR assay was used to select the sh-CXCL8-13 group lentivirus as the intervention sequence and virus for subsequent experiments.The experiments were divided into the blank control group,negative control group,sh-CXCL8 group,paclitaxel group,and sh-CXCL8+paclitaxel group.The proliferative activity and invasive ability of cervical cancer cells were assessed by CCK-8 and cell invasion assays.The expression of CXCL8,Bcl2,Bax,and β-actin were detected by qRT-PCR and Western blot. Results Compared with the other four groups,the proliferative and invasive ability of Hela cells was significantly reduced in the sh-CXCL8+paclitaxel group,and the difference was statistically significant(P＜0.01).The qRT-PCR results showed that the expression of CXCL8,Bcl2,PIK3CB,and Akt1 genes was significantly reduced,and the expression of Bax gene was significantly increased in the sh-CXCL8+paclitaxel group.The difference between the groups was statistically significant(P＜0.001).The results of Western blot showed that the expression of CXCL8,PIK3CB,and p-Akt1 proteins was reduced in the sh-CXCL8+paclitaxel group(P＜0.05). Conclusion Knocking down CXCL8 can reduce the proliferative and invasive capacity of Hela cells,possibly by affecting the PI3K/Akt pathway to affect the drug sensitivity of Hela cells to paclitaxel.

Key words: Cervical cancer, CXCL8, Paclitaxel, Sensitivity, Invasion

中图分类号:

R737.33

张华, 努尔比亚·依比布拉, 路鹏霏, 贾春丽, 裴轩萱, 包永星. CXCL8对宫颈癌细胞紫杉醇敏感性的影响及机制研究[J]. 实用肿瘤学杂志, 2025, 39(1): 13-20.

ZHANG Hua, Nurbia Ibibulla, LU Pengfei, JIA Chunli, PEI Xuanxuan, BAO Yongxing. Effect and mechanism of CXCL8 on the paclitaxel sensitivity of cervical cancer cells[J]. Journal of Practical Oncology, 2025, 39(1): 13-20.

参考文献

1 Voelker RA.Cervical cancer screening[J].JAMA,2023,330(20):2030.
2 Ang DJM,Chan JJ.Evolving standards and future directions for systemic therapies in cervical cancer[J].J Gynecol Oncol,2024,35(2):e65.
3 张艺艺,李奇,刘旭,等.宫颈癌患者五年生存及影响因素分析[J].实用肿瘤学杂志,2022,36(1):7-13.
4 Abu-Rustum NR,Yashar CM,Arend R,et al.NCCN Guidelines^®Insights:cervical cancer,version 1.2024[J].J Natl Compr Canc Netw,2023,21(12):1224-1233.
5 Ahmed Khalil A,Rauf A,Alhumaydhi FA,et al.Recent developments and anticancer therapeutics of paclitaxel:an update[J].Curr Pharm Des,2022,28(41):3363-3373.
6 Smycz-Kubańska M,Stępień S,Gola JM,et al.Analysis of CXCL8 and its receptors CXCR1/CXCR2 at the mRNA level in neoplastic tissue,as well as in serum and peritoneal fluid in patients with ovarian cancer[J].Mol Med Rep,2022,26(4):296.
7 Yi M,Peng C,Xia B,et al.CXCL8 facilitates the survival and paclitaxel-resistance of triple-negative breast cancers[J].Clin Breast Cancer,2022,22(2):191-198.
8 Zhang J,Yin Y,Tang J,et al.Changes in serum interleukin-8 levels predict response to immune checkpoint inhibitors immunotherapy in unresectable hepatocellular carcinoma patients[J].J Inflamm Res,2024,17:3397-3406.
9 Walle T,Kraske JA,Liao B,et al.Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8[J].Sci Adv,2022,8(12):eabh4050.
10 Han D,Zhang N,Zhao S,et al.AKIP1 promotes glioblastoma viability,mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways[J].Am J Cancer Res,2021,11(4):1185-1205.
11 Gopu P,Antony F,Cyriac S,et al.Updates on systemic therapy for cervical cancer[J].Indian J Med Res,2021,54(2):293-302.
12 Wu T,Yang W,Sun A,et al.The role of CXC chemokines in cancer progression[J].Cancers(Basel),2022,15(1):167.
13 Raza S,Rajak S,Tewari A,et al.Multifaceted role of chemokines in solid tumors:From biology to therapy[J].Semin Cancer Biol,2022,86(Pt 3):1105-1121.
14 Fu X,Wang Q,Du H,et al.CXCL8 and the peritoneal metastasis of ovarian and gastric cancer[J].Front Immunol,2023,14:1159061.
15 Khera N,Rajkumar AS,Abdulkader M Alkurdi K,et al.Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells[J].Mol Cancer,2023,22(1):146.
16 Yang S,Wang H,Qin C,et al.Up-regulation of CXCL8 expression is associated with a poor prognosis and enhances tumor cell malignant behaviors in liver cancer[J].Biosci Rep,2020,40(8):BSR20201169.
17 Shao Y,Lan Y,Chai X,et al.CXCL8 induces M2 macrophage polarization and inhibits CD8+ T cell infiltration to generate an immunosuppressive microenvironment in colorectal cancer[J].FASEB J,2023,37(10):e23173.

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CXCL8对宫颈癌细胞紫杉醇敏感性的影响及机制研究

Effect and mechanism of CXCL8 on the paclitaxel sensitivity of cervical cancer cells

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