[1]欧艺虹,姜耀东,李琦,等.肥大细胞通过上调p21促进前列腺癌神经内分泌分化及增加对多西他赛化疗的抵抗性[J].南方医科大学学报,2018,(06):723.
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肥大细胞通过上调p21促进前列腺癌神经内分泌分化及增加对多西他赛化疗的抵抗性()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2018年06期
页码:
723
栏目:
出版日期:
2018-06-30

文章信息/Info

Title:
Infiltrating mast cells promote neuroendocrine differentiation and increase docetaxel resistance of prostate cancer cells by up-regulating p21
作者:
欧艺虹姜耀东李琦庄永江党强谭万龙
关键词:
前列腺癌肥大细胞神经内分泌分化p21多西他赛
Keywords:
prostate cancer neuroendocrine differentiation mast cells p21 docetaxel
摘要:
目的探索肥大细胞浸润对前列腺癌细胞神经内分泌分化(NED)及多西他赛化疗敏感性的影响。方法利用Transwell小 室将人前列腺癌细胞系(LNCaP和C4-2)与人肥大细胞系(HMC-1)进行共培养,通过sh-AR慢病毒沉默C4-2细胞AR的表达, 通过sh-p21质粒(pLKO.1-sh-p21)和p21过表达质粒(pCMV-p21)转染分别沉默和过表达前列腺癌细胞p21,倒置显微镜观察 LNCaP和C4-2细胞的形态变化,MTT实验及克隆形成实验检测LNCaP和C4-2的细胞增殖能力,CCK8实验检测C4-2在多西 他赛化疗下的细胞活性,RT-qPCR实验及Western blot实验分别检测前列腺癌细胞细胞神经内分泌标志物、AR、p21的mRNA 及蛋白表达量。结果HMC-1细胞共培养可以增加LNCaP和C4-2细胞的NE表型表达,抑制LNCaP和C4-2细胞的增殖能力, 并上调p21的表达(P<0.05)。P21通过不依赖AR的信号通路正向调控前列腺癌细胞NED,敲除p21表达可部分逆转HMC-1共 培养促进NED的作用。同时,肥大细胞共培养后的前列腺癌细胞对多西他赛化疗的抵抗性增加(P<0.05),敲除p21部分逆转了 肥大细胞提高多西他赛化疗抵抗性的作用。结论肥大细胞可以部分通过上调p21表达促进前列腺癌细胞NED以及增加对多 西他赛化疗的抵抗性。
Abstract:
Objective To investigate the effect of infiltrating mast cells on neuroendocrine differentiation (NED) and docetaxel sensitivity of prostate cancer (PCa) cells in vitro. Methods Human PCa cell lines (LNCaP and C4-2) were co-cultured with human mast cell line (HMC-1) in Transwell chambers. Androgen receptor (AR) was silenced in C4-2 cells using sh-AR lentivirus, and p21 was knocked down and overexpressed by transfecting C4-2 cells with pLKO.1-sh-p21 and pCMV-p21, respectively. The morphological changes of LNCaP and C4-2 cells were observed. MTT assay and colony formation assay were used to assess the proliferation of LNCaP and C4-2 cells. CCK8 assay was used to detect the cell viability of C4-2 cells following docetaxel trreatment. RT-qPCR and Western blotting were performed to determine the mRNA and protein expressions of neuroendocrine markers, AR and p21 in the cells. Results Co-culture with HMC-1 cells enhanced the neuroendocrine phenotypes, inhibited the proliferation and up-regulated the expression of p21 in LNCaP and C4-2 cells. P21 positively regulated NED through a non-AR-dependent signaling pathway, while p21 knockdown partially reversed NED promoted by the mast cells. PCa cells co-cultured with HMC-1 cells showed increased resistance to docetaxel, and silencing p21 partially reversed docetaxel resistance in PCa cells. Conclusion Infiltrating mast cells up-regulates p21 to promote NED and increase docetaxel resistance in PCa cells in vitro.

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更新日期/Last Update: 1900-01-01