Notch3增强三阴性乳腺癌MDA-MB-231细胞对顺铂的敏感性

doi:10.3969/j.issn.1004-616x.2016.02.006

Abstract

Abstract: OBJECTIVE: To investigate the effect of stem cell-related factor, Notch3 on human triple negative breast cancer cell, MDA-MB-231 and its resistance to cisplatin, and explore if overexpressed Notch3 can enhance the sensitivity of resistance cells to cisplatin. METHODS: Lipofectamine 2000 was applied to transfect Notch3 plasmid into MDA-MB-231. These cells were divided into MDA-MB-231-PCLE group and MDA-MB-231-N3ICD group, according to the use of different plasmids. RT-PCR and Western blot methods were used to analyze the expression of Notch3 in different groups. The effects of cisplatin on cell proliferation were assessed by CCK8 assay and evaluated by GraphPad Prism 5. Lipofectamine 2000 was also applied to transfect the siNotch3 or scramble to cells and they were divided into T47D-NC and T47D-siNotch3 groups. The protein levels of apoptosis-related factor were detected using RT-PCR methods and Western blot. RESULTS: Then efficacy of cisplatin to triple negative breast cancer cells was enhanced by overexpression of Notch3. Apoptosis-related factor, caspase-3 was up-regulated by Notch3 overexpression. However, siNotch3 induced the downregulation of caspase-3 in T47D, in which the expression of Notch3 was high. CONCLUSION: Overexpression of Notch3 enhanced the sensitivity of MDA-MB-231 to cisplatin which suggests that this may improve the efficiency of chemotherapy in patients with breast cancer.

Key words: Notch3, cisplatin, breast cancer, chemotherapy

CLC Number:

WU Huatao, SHEN Jiaxin, LIU Jing. Overexpression of Notch3 enhance the efficacy of cisplatin to MDA-MB-231[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(2): 111-114,120.

References

[1] Siegel RL,Miller KD,Jemal A. Cancer statistics,2015[J]. CA Cancer J Clin,2015,65(1):5-29.
[2] Takebe N,Miele L,Harris PJ,et al. Targeting Notch, Hedgehog,and Wnt pathways in cancer stem cells:clinical update[J]. Nat Rev Clin Oncol,2015,12(8):445-464.
[3] Man CH,Wei-Man Lun S,Wai-Ying Hui J,et al. Inhibition of Notch3 signalling significantly enhances sensitivity to cisplatin in EBV-associated nasopharyngeal carcinoma[J]. J Pathol, 2012,226(3):471-481.
[4] Dang L,Yoon K,Wang M,et al. Notch3 signaling promotes radial glial/progenitor character in the mammalian telencephalon[J]. Dev Neurosci,2006,28(1/2):58-69.
[5] Porter AG,Janicke RU. Emerging roles of caspase-3 in apoptosis[J]. Cell Death Differ,1999,6(2):99-104.
[6] Lobry C,Oh P,Mansour MR,et al. Notch signaling:switching an oncogene to a tumor suppressor[J]. Blood,2014, 123(16):2451-2459.
[7] Xu J,Song F,Jin T,et al. Prognostic values of Notch receptors in breast cancer[J]. Tumor Biol,2015:1-7.
[8] Yen WC,Fischer MM,Axelrod F,et al. Targeting Notch signaling with a Notch2/Notch3 antagonist (tarextumab) inhibits tumor growth and decreases tumor-initiating cell frequency[J]. Clin Cancer Res,2015,21(9):2084-2095.
[9] Du X,Zhao YP,Zhang TP,et al. Alteration of the intrinsic apoptosis pathway is involved in Notch-induced chemoresistance to gemcitabine in pancreatic cancer[J]. Arch Med Res,2014, 45(1):15-20.
[10] McAuliffe SM,Morgan SL,Wyant GA,et al. Targeting Notch,a key pathway for ovarian cancer stem cells,sensitizes tumors to platinum therapy[J]. Proc Natl Acad Sci USA, 2012,109(43):2939-2948.
[11] Savage P,Stebbing J,Bower M,et al. Why does cytotoxic chemotherapy cure only some cancers?[J]. Nat Clin Pract Oncol,2009,6(1):43-52.
[12] Choudhary GS,Al-Harbi S,Almasan A. Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis[J]. Methods Mol Biol,2015,1219:1-9.

[1]	XIN Yumeng, LIANG Huanxi, YU Yuehua, SUN Zhenxiao. Network pharmacology and molecular docking mechanisms of licorice and dried ginger decoction against breast cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 7-13.
[2]	ZHAO Yan, SUN Zhenxiao. Metformin inhibitd proliferation and migration of human breast cancer cell in vitro [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 35-39.
[3]	FANG Yutong, ZHANG Qunchen, HONG Chaoqun, CHEN Chunfa, CHEN Jiongyu, ZHANG Rendong, WU Jundong. Mechanisms of miR-221 and miR-222 on expression of GATA3 and FOXA1 and their effects in breast cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 435-441,460.
[4]	ZHANG Shimin, ZHAO Ruijun. Expression of protein tyrosine phosphatase receptor J in breast cancer tissues and its relationship with clinical prognosis [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 276-279,285.
[5]	CHENG Bin, WANG Xinyu, SUN Yu, ZHANG Jiatai, DONG Shuying. Inhibition of metformin on phthalate-induced proliferation and migration of MCF-7 breast cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 197-202.
[6]	LUO Jiao, ZHANG Kunchi, ZHOU Li. Analysis of differentially expressed microRNAs between the triple negative breast cancer cell line MDA-MB-231 and its brain metastasis cell line [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 218-224.
[7]	ZHANG Yuling, WU Jundong, PANG Dongyue, CHEN Chunfa. Changes of Ki67 expression before and after neoadjuvant chemotherapy as a predictor for therapeutic response and rognosis in breast cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 230-235,245.
[8]	LI Weiwei, ZHU Ying. Data mining analyses of expression and prognostic values of the MYB family in breast cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 414-422.
[9]	CHEN Mianling, MA Shuoyi. Regulation of migration and invasion of triple-negative breast cancer cell MDA-MB-231 by miR-21 via targeting PDCD4 [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 292-297.
[10]	ZHANG Huijuan, HUANG Dayuan, ZHANG Jie, TANG Haiou, XIE Anxin, TAN Dunyong. Effects of SF1a-PRLR and ΔS2 SF1a-PRLR on proliferation and microRNA expressionin MCF-7 breast cancer cell [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 203-208.
[11]	SUN Quanwu, DU Xiaoping, HAO Jie, SHI Rong, LIU Bo, HUANG Haiyun. β1 integrin expression in breast cancer patients with pathological nipple discharge [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(5): 368-372.
[12]	WANG Lan, ZHANG Yongdong, GUO Hongyun, WANG Tao, WANG Haitao, GUO Huan, YANG Suisheng, LI Xiaoqin, SU Haixiang. Relationships between XRCC3 polymorphisms and breast cancer in northern Chinese women [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(5): 392-396,400.
[13]	WAN Shuquan, WEI Lijun, WANG Fuhua, ZENG Yong. Expression of miR-200b-3p and PAK2 in chemotherapy-resistant and sensitive ovarian cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 216-221.
[14]	DU Juan, HU Xiangyang, LIU Dan, HU Wei, CHEN Tao. Inhibitory effect of total alkaloids of Tougucao on bone metastasis of breast cancer cells in mice [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(6): 435-441.
[15]	WANG Yuqiang, LI Hongjuan, JIANG Tianliang, CAO Yifei, YANG Jun. Involvement of UBE2A in cisplatin-induced stress response in HeLa cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(6): 463-467.

Overexpression of Notch3 enhance the efficacy of cisplatin to MDA-MB-231

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments