CDK4/6抑制剂阿贝西利联合顺铂对人胃癌细胞生物学行为的影响

doi:10.3969/j.issn.1004-616x.2024.05.008

Abstract

Abstract: OBJECTIVE： To investigate biological behavior of human gastric cancer cells after their treatment with the CDK4 and CDK6 (CDK4/6) inhibitor abemaciclib，and cisplatin. METHODS： The TCGA database resources and the bioinformatics UALCAN website were used to obtain the expression of CDK4/6 genes in gastric cancers and normal gastric tissues. Western blot test was used to detect expression of CDK4 and CDK6 albumen in the stomach-carcinoma cell line SGC7901 and the regular gastric mucous membrane cell line GES-1. The CCK-8 method was used to screen for the optimal cell growth inhibition concentration. The cells were divided into several groups：blank control，0.5 μg/mL cisplatin，10 μmol/L abemaciclib+0.5 μg/mL cisplatin，and 10 μmol/L abemaciclib groups. These groups were treated for 24，48 and 72 h. Then CCK-8 method，flow cytometry，scratch assay and Transwell assay were used to detect the proliferation，apoptosis，migration and invasion gastric cancer cells SGC-7901 in each subgroup RESULTS： Based on bioinformatics analysis， expression of CDK4/6 proteins in human gastric cancer tissues was significantly higher than that in normal gastric tissues (P<0.05). Western blot analyses showed that expression of CDK4/6 proteins was significantly increased in SGC7901 compared with that in normal tissues (P<0.05). According to the CCK-8 results，the cisplatin concentration for the IC₅₀ value was 0.5 μg/mL and the abemaciclib was 10 μmol/L，therefore these concentrations were used for subsequent experiments. Compared with the blank control group，the combined treatment inhibited cell proliferation significantly (P<0.01)，and the inhibition ability was time-dependent(r=0.949，P<0.01). The level of apoptosis was significantly increased (P<0.01)，and both migration and invasion capacity were significantly reduced (P<0.01). CONCLUSION： Expression of CDK4/6 was significantly increased in human gastric cancer tissues and cells. Combined treatment of these cells with abemaciclib and cisplatin showed synergistic effects，which significantly inhibited the proliferation，migration，invasion of human gastric cancer cells and promoted apoptosis.

Key words: CDK4/6, gastric cancer, abemaciclib, cisplatin, biological behavior

CLC Number:

R735.2

DI Rongwei, FU Xinya, MA Xiumei, LI Chao, HAI Ling. Effects of CDK4/6 inhibitor abemaciclib and cisplatin on biological behavior of human gastric cancer cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(5): 384-390.

References

[1] QI J L, LI M L, WANG L J, et al. National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data[J]. Lancet Public Health, 2023, 8(12): 943-955.
[2] FASSL A, GENG Y, SICINSKI P. CDK4 and CDK6 kinases: from basic science to cancer therapy[J]. Science, 2022, 375(6577): eabc1495.
[3] ADON T, SHANMUGARAJAN D, KUMAR H Y. CDK4/6 inhibitors: a brief overview and prospective research directions[J]. RSC Adv, 2021, 11(47): 29227-29246.
[4] GAO X L, LEONE G W, WANG H Z. Cyclin D-CDK4/6 functions in cancer[J]. Adv Cancer Res, 2020, 148: 147-169.
[5] SHERR C J, BEACH D, SHAPIRO G I. Targeting CDK4 and CDK6: from discovery to therapy[J]. Cancer Discov, 2016, 6(4): 353-367.
[6] NEBENFUEHR S, KOLLMANN K, SEXL V. The role of CDK6 in cancer[J]. Int J Cancer, 2020, 147(11): 2988-2995.
[7] VIJAYARAGHAVAN S, MOULDER S, KEYOMARSI K, et al. Inhibiting CDK in cancer therapy: current evidence and future directions[J]. Target Oncol, 2018, 13(1): 21-38.
[8] KLEIN M E, KOVATCHEVA M, DAVIS L E, et al. CDK4/6 inhibitors: the mechanism of action may not be as simple as once thought[J]. Cancer Cell, 2018, 34(1): 9-20.
[9] VERMEULEN K, VAN BOCKSTAELE D R, BERNEMAN Z N. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer[J]. Cell Prolif, 2003, 36(3): 131-149.
[10] GOEL S, DECRISTO M J, WATT A C, et al. CDK4/6 inhibition triggers anti-tumour immunity[J]. Nature, 2017, 548(7668): 471-475.
[11] SLEDGE G W Jr, TOI M, NEVEN P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR⁺/HER²^- advanced breast cancer who had progressed while receiving endocrine therapy[J]. J Clin Oncol, 2017, 35(25): 2875-2884.
[12] BRAAL C L, JONGBLOED E M, WILTING S M, et al. Inhibiting CDK4/6 in breast cancer with palbociclib, ribociclib, and abemaciclib: similarities and differences[J]. Drugs, 2021, 81(3): 317-331.
[13] HAMILTON E, CORTES J, OZYILKAN O, et al. nextMONARCH: abemaciclib monotherapy or combined with tamoxifen for metastatic breast cancer[J]. Clin Breast Cancer, 2021, 21(3): 181-190.e2.
[14] JOHNSTON S R D, HARBECK N, HEGG R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR⁺, HER²^-, node-positive, high-risk, early breast cancer (monarchE)[J]. J Clin Oncol, 2020, 38(34): 3987-3998.
[15] DHIR T, SCHULTZ C W, JAIN A, et al. Abemaciclib is effective against pancreatic cancer cells and synergizes with HuR and YAP1 inhibition[J]. Mol Cancer Res, 2019, 17(10): 2029-2041.
[16] LIU Y, ZHAO R S, FANG S S, et al. Abemaciclib sensitizes HPV-negative cervical cancer to chemotherapy via specifically suppressing CDK4/6-Rb-E2F and mTOR pathways[J]. Fundam Clin Pharmacol, 2021, 35(1): 156-164.
[17] O’LEARY B, FINN R S, TURNER N C. Treating cancer with selective CDK4/6 inhibitors[J]. Nat Rev Clin Oncol, 2016, 13(7): 417-430.
[18] GOEL S, BERGHOLZ J S, ZHAO J J. Targeting CDK4 and CDK6 in cancer[J]. Nat Rev Cancer, 2022, 22(6): 356-372.
[19] DIGIACOMO G, FUMAROLA C, LA MONICA S, et al. CDK4/6 inhibitors improve the anti-tumor efficacy of lenvatinib in hepatocarcinoma cells[J]. Front Oncol, 2022, 12: 942341.
[20] 郭晶晶, 牟迪, 于文文, 等. Abemaciclib抑制c-Myc高表达小细胞肺癌增殖、侵袭和迁移的生物学功能的研究[J]. 中国肺癌杂志, 2023, 26(2): 105-112.

Effects of CDK4/6 inhibitor abemaciclib and cisplatin on biological behavior of human gastric cancer cells

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	XUE Song, HU Jiahai, DONG Xiangning. Expression of PGAM5 and its association with clinicopathologic characteristics in pancreatic cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(1): 29-34.
[2]	HUANG Conggai, LIU Qing, ZHENG Shutao, LIU Tao, TAN Yiyi, PENG Tianyuan, CHEN Jiao, LU Xiaomei. Expression of CXCR2 in esophageal cancer tissues and its impact on biological behavior of esophageal cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(1): 53-57,65.
[3]	HE Guangsi, WEI Jie, ZHANG Jian. Usefulness for combined detection of serum miRNA-183 and carbohydrate antigen 199 in the diagnosis and prognosis of gastric cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(6): 457-461,466.
[4]	QIN Jingna, ZHOU Yingfa, LIU Heyong. Diagnostic values from combined detection of both inflammatory and tumor markers for preoperative gastric cancer staging [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(2): 139-143.
[5]	XU Hao, HU Bichuan, ZOU Wei, DUAN Yabin. Identification of prognostic factors among patients with stage Ⅲ gastric cancer undergoing radical resection [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(1): 30-36.
[6]	QI Jiankao, TANG Xiao, SUN Shihui, KOU Yanfang, CUI Zhiqin. Growth inhibition of non-small cell lung cancers by Zaoci decotion in combination with cisplatin and gemcitabine [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(5): 366-372,403.
[7]	YU Yuehua, LIANG Huanxi, XIN Yumeng, SUN Zhenxiao. Investigations on anti-gastric cancer effects of licorice and dried ginger decoction [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(3): 219-226.
[8]	YANG Chanjun, CHEN Wentian, LIU Jing. Bioinformatics analysis of gastric cancer datasets regarding collagen as a possible biomarker [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 410-419.
[9]	CUI Zhaoyang, LI Suna, JIANG Xuqian, WANG Yidan, HOU Liying. Activation of the TRAIL death receptor by apigenin for induction of apoptosis in the gastric cancer SGC-7901 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 32-36.
[10]	LIU Peng, BAI Yixiao. Effect of miR-29a on proliferation and migration of human gastric cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 452-456,463.
[11]	Lü Yanping, WU Chuancheng, YANG Shuangfeng, HE Chenzhou, HAN Renjie, YAN Wei, LIU Baoying. Relationship between differentially expressed miRNA-SNPs and prognosis of gastric cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 380-386.
[12]	WANG Yaojie, XIANG Xiaohan, HAN Lina, LI Jun, HUO Bingjie, ZHAO Lianmei. Inhibitory effects of ethanol extract from Euphorbia humifusa on gastric cancer cells in vitro [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 187-193.
[13]	LI Dan, LIU Baoying, YU Mingming, ZHUANG Hailin, JIE Jinhua, WU Hanmei. NFKBIA polymorphism, eating habits and susceptibility to gastric cancer: a case-control study [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 198-202.
[14]	SHEN Zhihua, HUANG Sachula, MA Xiumei. Expression of heparanase, E-cadherin, N-cadherin and vimentin in gastric cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(2): 98-104.
[15]	SHU Zhixiong, WU Chuancheng, WU Xiaoli, LIU Baoying. Relationships between gastric cancer and SNPs of autophagy-related genes on the PI3K/Akt/mTOR pathway [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(2): 118-125,131.