PCDH10 prevents multiple myeloma cell escape from epirubicin-induced cytotoxicity

Yuan Haiting; Chen Jianbin; Xu Yonghui; Yang Zesong

doi:10.13406/j.cnki.cyxb.000849

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PCDH10 prevents multiple myeloma cell escape from epirubicin-induced cytotoxicity

更新时间：2024-01-17

- PCDH10 prevents multiple myeloma cell escape from epirubicin-induced cytotoxicity
- Journal of Chongqing Medical University Vol. 41, Issue 4, Pages: 388-392(2016)
- 作者机构：
  
  重庆医科大学附属第一医院血液科
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.000849
  CLC： R733.3
- Published：2016，
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[1]袁海汀,陈建斌,许永会,杨泽松.PCDH10减少多发性骨髓瘤细胞逃避表阿霉素杀伤[J].重庆医科大学学报,2016,41(04):388-392.

Yuan Haiting, Chen Jianbin, Xu Yonghui, et al. PCDH10 prevents multiple myeloma cell escape from epirubicin-induced cytotoxicity. [J]. Journal of Chongqing Medical University 41(4):388-392(2016)
[1]袁海汀,陈建斌,许永会,杨泽松.PCDH10减少多发性骨髓瘤细胞逃避表阿霉素杀伤[J].重庆医科大学学报,2016,41(04):388-392. DOI： 10.13406/j.cnki.cyxb.000849.

Yuan Haiting, Chen Jianbin, Xu Yonghui, et al. PCDH10 prevents multiple myeloma cell escape from epirubicin-induced cytotoxicity. [J]. Journal of Chongqing Medical University 41(4):388-392(2016) DOI： 10.13406/j.cnki.cyxb.000849.

摘要

目的:探讨原钙黏蛋白10（protocadherin-10

PCDH10）对表阿霉素杀伤多发性骨髓瘤（multiple myeloma

MM）细胞的影响及机制。方法:采用脂质体法将PCDH10基因转染入人MM细胞株RPMI8226细胞

RT-PCR和Western blot法检测PCDH10基因和蛋白的表达;CCK-8法检测表阿霉素对RPMI8226细胞的增殖抑制作用

求得半数抑制浓度（half-maximal inhibitory concentration

IC50）;Transwell法检测表阿霉素和PCDH10对RPMI8226细胞迁移的影响;流式细胞术检测CXC族趋化因子受体4（CXC chemokine receptor 4

CXCR4）蛋白表达;Western blot方法检测Ras同源家族成员A（ras homolog gene family member A

Rho A）和基质金属蛋白酶9（matrix metalloproteinase-9

MMP-9）蛋白表达情况。结果:PCDH10基因成功转染入RPMI8226细胞

并成功表达;PCDH10转染组表阿霉素IC50为（0.87±0.07）μg/ml

明显低于空质粒转染组（1.27±0.02）μg/ml（F=77.93

P=0.000）;PCDH10减少表阿霉素所致的细胞迁移（F=34.943

P=0.000）并抑制CXCR4（F=117.269

P=0.000）、Rho A（F=1 818.250

P=0.000）和MMP-9（F=523.764

P=0.000）蛋白表达。结论:PCDH10一方面可增强MM细胞对表阿霉素的敏感性

另一方面可通过抑制CXCR4、Rho A、MMP-9蛋白的表达来减少MM细胞逃避表阿霉素的杀伤

从而增强了表阿霉素的抗骨髓瘤效应。

Abstract

Objective:To explore the influence and mechanism of PCDH10 on the chemotherapy of epirubicin in multiple myeloma(MM). Methods:The PCDH10 expression was regulated by transfecting pc DNA3.1(+)PCDH10 in RPMI8226 cells. RT-PCR and Western blot were used to test the transfection effect. The CCK-8 assay was used to evaluate cell proliferation. The Boyden chamber and matrigel glue were used to construct migration and invasion model for detecting the influence of PCDH10 on epirubicin-induced cell escape. Flow cytometry was used to test the CXCR4 protein expression. Western blot was used to assess the expression of Rho A and MMP-9. Results:The m RNA and protein expressions of PCDH10 were significantly up regulated by pc DNA3.1(+)-PCDH10.Epirubicin could inhibit cell proliferation in a dose-ependent manner but the IC50 for PCDH10-transfected cells(0.87±0.07)μg/ml was much lower than that for vector-transfected cells(1.27±0.02)μg/ml(F=77.93

P=0.000). The effect that epirubicin could induce cell escape could be inhibited by PCDH10(F=34.943

P=0.000). The expression of CXCR4 which could be stimulated by epirubicin was decreased by PCDH10(F=117.269

P=0.000). PCDH10 could also reduce the expression of Rho A(F=1 818.250

P=0.000)and MMP-9(F=523.764

P=0.000)obviously. Conclusion:PCDH10 could sensitize RPMI8226 cells to epirubicin and inhibit epirubicininduced cell escape. The down-regulating of CXCR4

Rho A and MMP-9 may act as an important mechanism.

关键词

多发性骨髓瘤PCDH10基因表阿霉素CXC族趋化因子受体4Ras同源家族成员A基质金属蛋白酶9

Keywords

multiple myelomaprotocadherin-10EpirubicinCXC chemokine receptor 4ras homolog gene family member Amatrix metalloproteinase-9

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