Effects of PHA-767491 on the inhibition of CDC-7 expression in endometrial cancer ishikawa cell line

doi:10.12092/j.issn.1009-2501.2019.08.004

Abstract

Abstract:

AIM: To investigate the effects of PHA-767491 on the inhibition of CDC7 expression on proliferation, invasion, migration and apoptosis of endometrial cancer ishikawa cell line. METHODS: Different concentrations of PHA-767491 were used to treat the endometrial cancer ishikawa cell line. The proliferation ability of ishikawa cells and the IC50 were determined by CCK-8 method. RT-PCR was used to detect the effect of PHA-767491 on the expression of CDC-7 mRNA in ishikawa cells. The migration ability of the cells was then examined using a scratch test. The transwell chamber method was applied to detect the invasive ability of ishikawa cells.Flow cytometry Annexin V/PI double staining was used to detect cell apoptosis. RESULTS:The results of CCK-8 assay showed that PHA-767491 significantly inhibited the proliferation of endometrial cancer ishikwa cells with an IC50 of 9.51 μmol/L at 24 hours. RT-PCR showed that PHA-767491 significantly inhibited the expression of Cdc-7 mRNA in ishikawa cells. Scratch test showed that PHA-767491 effectively inhibited the migration ability of ishikawa cells. Transwell chamber results showed that PHA-767491 inhibited the invasion of ishikawa cells.PHA-767491 significantly induced ishikawa cells apoptosis.CONCLUSION: PHA-767491 can significantly inhibit the expression of CDC-7 in ishikawa of endometrial cancer cells, which can significantly reduce the proliferation, migration and invasion and induce apoptosis of ishikawa cells.

Key words: PHA-767491, CDC-7, endometrial cancer, proliferation, migration, invasion, apoptosis

CLC Number:

R737.3

WANG Qingwei, DING Jin, LV Yuanyuan, LUO Xianchen, NI Guantai. Effects of PHA-767491 on the inhibition of CDC-7 expression in endometrial cancer ishikawa cell line[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(8): 866-871.

References

［1］Wójcik-Krowiranda KM, Szczepaniec S, Bieńkiewicz A. The role of the βKlotho gene in uterine endometrial cancer［J］. Ginekol Pol, 2018, 89(10): 563-567.
［2］Packer LM, Stehbens SJ, Bonazzi VF, et al. Bcl-2 inhibitors enhance FGFR inhibitor-induced mitochondrial-dependent cell death in FGFR2 mutant endometrial cancer［J］. Mol Oncol, 2019 ,13(4):738-756.
［3］Tenca P, Brotherton D, Montagnoli A, et al. CDC7 is an active kinase in human cancer cells undergoing replication stress［J］. J Biol Chem, 2007,282(1):208-215.
［4］Tudzarova S, Mulholland P, Dey A, et al. p53 controls CDC7 levels to reinforce G1 cell cycle arrest upon genotoxic stress［J］. Cell Cycle, 2016,15(21):2958-2972.
［5］Li W, Zhao XL, Shang SQ, et al. Dual inhibition of Cdc7 and Cdk9 by PHA-767491 suppresses hepatocarcinoma synergistically with 5-Fluorouracil［J］. Curr Cancer Drug Targets, 2015, 15(3):196-204.
［6］徐瑞云，严晓丽，石建芹,等. CDC7和MCM4在子宫内膜腺癌中的表达及意义［J］.中国妇幼保健,2016, 31(5):1048-1051.
［7］Moore K, Brewer MA. Endometrial cancer: Is this a new disease［J］. Am Soc Clin Oncol Educ Book, 2017,37:435-442.
［8］Sclafani RA, Holzen TM. Cell cycle regulation of DNA replication［J］. Annu Rev Genet, 2007,41:237-280.
［9］Labib K. How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells［J］? Genes Dev, 2010, 24(12):1208-1219.
［10］Kulkarni AA, Kingsbury SR, Tudzarova S, et al. Cdc7 kinase is a predictor of survival and a novel therapeutic target in epithelial ovarian carcinoma［J］. Clin Cancer Res, 2009,15(7):2417-2425.
［11］Melling N, Muth J, Simon R, et al. Cdc7 overexpression is an independent prognostic marker and a potential therapeutic target in colorectal cancer［J］. Diagn Pathol, 2015,10:125.
［12］Datta A, Ghatak D, Das S, et al. p53 gain-of-function mutations increase Cdc7-dependent replication initiation［J］. EMBO Rep, 2017, 18(11):2030-2050.
［13］Jaafari-Ashkavandi Z, Ashraf MJ, Abbaspoorfard AA. Overexpression of CDC7 in malignant salivary gland tumors correlates with tumor differentiation［J］. Braz J Otorhinolaryngol, 2019,85(2):144-149.
［14］Choschzick M, Lebeau A, Marx AH, et al. Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer［J］. Hum Pathol, 2010,41(3):358-365.
［15］Bonte D, Lindvall C, Liu H,et al. Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is correlated with p53 inactivation［J］. Neoplasia, 2008, 10(9):920-924.
［16］Montagnoli A, Tenca P, Sola F, et al. Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells［J］.Cancer Res, 2004,64(19):7110-7116.
［17］Im JS, Lee JK. ATR-dependent activation of p38 MAP kinase is responsible for apoptotic cell death in cells depleted of Cdc7［J］. J Biol Chem, 2008, 283(37):25171-25177.
［18］Sasi NK, Bhutkar A, Lanning NJ, et al. DDK Promotes tumor chemoresistance and survival via multiple pathways［J］.Neoplasia,2017,19(5):439-450.
［19］Swords R, Mahalingam D, O'Dwyer M, et al. Cdc7 kinase-a new target for drug development［J］. Eur J Cancer, 2010, 46(1):33-40.
［20］Montagnoli A, Moll J, Colotta F. Targeting cell division cycle 7 kinase:a new approach for cancer therapy［J］. Clin Cancer Res, 2010, 16(18):4503-4508.
［21］Montagnoli A, Valsasina B, Croci V, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity［J］.Nat Chem Biol, 2008,4(6):357-365.

[1]	FAN Jie, JIN Yongming, JIANG Xiaolong, JIANG Guohua. Molecular mechanism of lncRNA HOTAIR regulating miR-206 on the proliferation and apoptosis of rheumatoid arthritis synovial cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(7): 736-742.
[2]	YANG Xiaojia, JIANG Meng, WU Min, ZHANG Yili, LV Lan, WU Yuanfen, WANG Xinyu, LIU Liquan. Improvement effect of crocin on cognitive impairment of Alzheimer's disease rats through DKK3 regulation of GSK-3 β/β-Catenin pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(5): 489-497.
[3]	WANG Yan, ZHANG Jinhui, ZHAO Yongchen, LIU Hongxiang, LIU Yawei, MIAO Huanhuan, YANG Xincai. Sequoiaflavone inhibits stem cell properties such as proliferation and invasion of gastric cancer cells by down-regulating PI3K/AKT signaling pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(5): 508-513.
[4]	ZHANG Xuejiao, LIU Jieting, LI Luxin, CHEN Peijian, DING Minglu, SUN Mengwei, CHU Yanhui, ZHANG Zhen . Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(3): 257-265.
[5]	HOU Xiaoyu, LENG Yufang, CAO Xuefen, LV Xingjiao, HAN Xiaoxia, Janvier NIBARUTA, LIU Yongqiang. Network analysis and experimental verification of Schisandrin B reduces intestinal ischemia reperfusion injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(2): 147-154.
[6]	WANG Jian, SUN Yongdong, ZHOU Xingwei, LIU Lei, CHEN Long, TONG Xingke, ZHU Jiali. Baicalein promotes laryngeal cancer cell death and inhibits invasion via miR-125b-5p/IRF4 axis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(11): 1209-1218.
[7]	ZHU Ruifang, GUO Dongkai, ZHI Hui, JIANG Yiguo, ZHANG Yueling, QIAN Xiaoping, JI Shiliang. Exploring the mechanism of elemene synergistic bortezomib against multiple myeloma by ROS-NF-κB-p38MAPK pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(11): 1219-1226.
[8]	HUANG Hao, JIA Hong, WANG Xiaoshuang, ZHANG Lu, JIANG Hua. Effects of co-culture of dendritic cells loaded with MAGE-A3 antigen and cytokine-induced killer cells on tumor stem cells and malignant progression of endometrial cancer [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(1): 42-50.
[9]	ZHOU Huan, XU Ming, LI Bo, LIU Chunying, WANG Chun. PI3K/Akt/FOXO3a signaling pathway inducing protective autophagy promotes acquired lung adenocarcinoma resistance remodeling to DDP [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(9): 961-970.
[10]	HUA Haiyan, YAN Jie, QIN Yufen. Experimental study of schisandrin B attenuates acute myocardial ischemia injury in rats by inhibiting cardiomyocyte apoptosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(8): 848-856.
[11]	DING Jiamin, WANG Youdi, ZHAO Xiali, JIANG Genfeng, CHEN Siwen, HONG Chengcheng, LI Shuqin, HU Weihua. Study on the treatment of thin endometrium with growth hormone and vitamin E [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(8): 857-862.
[12]	SUI Yuxia, ZHUANG Jie, ZHUANG Min, HUANG Gui. Delicaflavone inhibits the invasion and migration of gefitinib-resistant lung cancer PC-9/GR cells by regulating epithelial-mesenchymal transition via PI3K/Akt/mTOR pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 614-621.
[13]	LI Xueheng, LI Long. Research progress on the relationship between melatonin and idiopathic pulmonary fibrosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 715-720.
[14]	WANG Xinli, XU Xiaqing, FANG Hanbing, GUO Yuzhong. Study of TPA on enhancing the anti-tumor effects of cisplatin and reducing its renal toxicity [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(5): 535-543.
[15]	SHI Jingbin, XIONG Yang. Research progress on interaction between tumor microenvironment and breast cancer cells leading to tumor metastasis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(5): 562-574.