PDOX与DOX对乳腺癌MCF-7细胞的杀伤作用比较及毒性研究

目的：比较PDOX与阿霉素(doxorubicin，DOX)对乳腺癌MCF-7细胞的杀伤作用，阐述PDOX可能的作用机制，同时研究PDOX对正常肝细胞LO2、肾小管细胞NRK52E的毒性。方法：用DOX及PDOX按一定的浓度梯度的分别处理乳腺癌MCF-7细胞，计算两种药物对MCF-7细胞的半数抑制浓度；用相同浓度梯度的DOX及PDOX处理人正常肝LO2细胞、大鼠肾小管上皮NRK-52E细胞，比较PDOX、DOX对LO2、NRK-52E的毒性大小。流式细胞术分析PDOX、DOX处理后MCF-7细胞的周期分布情况；采用TUNEL、Hoechst染色、对PDOX、DOX处理后的MCF-7细胞进行细胞凋亡相关形态学分析并计算凋亡细胞比例。结果：DOX、PDOX处理MCF-7细胞48 h后，对MCF-7细胞的IC50分别为0.94、3.91μM；72 h时IC50分别为0.63、1.62μM。体外实验显示PDOX对LO2、NRK-52E细胞的细胞毒性较DOX小；PDOX处理后的细胞周期被阻滞在G1/S期；PDOX及DOX处理后的细胞表现出明显的凋亡细胞特点；1.96、3.91μM DOX或者1.96、3.91μM PDOX处理48 h后，各组的细胞凋亡率分别为46.1%、61.1%、41.3%及48.1%。结论：PDOX在体外诱导MCF-7细胞凋亡的能力较相同浓度的DOX弱；PDOX对LO2、NRK-52E细胞的毒性较DOX小。

The antitumor effect of PDOX and DOX on breast cancer MCF-7 cells and to assess the cytotoxicity

Objective: To evaluate the antitumor effect of PDOX on breast cancer MCF-7 cells, and to assess the cytotoxicity of PDOX on normal human hepatic cell line LO2 and mice renal tubal epithelium cell line NRK52E.Methods:Breast cancer MCF-7 cells were treated with different concentration of DOX or PDOX for indicated time, the half maximal inhibitory concentration (IC50) of DOX and PDOX were calculated for comparison; normal hepatic cell line LO2 and mice renal tubal epithelium cell line NRK-52E were treated with the identical concentration gradient of DOX or PDOX, and the cytotoxic effect of DOX or PDOX on LO2 cells and NRK52E cells were compared; cell cycle distribution of MCF-7 cells was analysed by lfow cytometry atfer being treated with identical concentration of DOX and PDOX; MCF-7 cells were treated with the identical concentration of DOX and PDOX, then the post-treatment morphology was determined by TdT-mediated dUTP nick end labeling (TUNEL), apoptotic cell Hoechst stain.Results: At 48 h, the IC50 of DOX and PDOX for MCF-7 cells were 0.94, 3.91 μM respectively; At 72 h, the IC50 of DOX and PDOX for MCF-7 cells were 0.63, 1.62 μM respectively. In vitro studies showed that PDOX had reduced cytotoxicity on LO2 cells and NRK52E cells compared with DOX; PDOX mainly arrested cell cycle of MCF-7 cells at G1/S phase. After PDOX and DOX treatment, MCF-7 cells revealed typical morphological characteristics and DNA fragmentation. Atfer being treated with 1.96, 3.91 μM DOX or 1.96, 3.91 μM PDOX for 48 h, the apoptotic rates were 46.1%, 61.1%, 41.3% and 48.1%, respectively.Conclusion: In vitro, PDOX had lesser anti-tumor effect on MCF-7 cells than equivalent DOX. Compared with DOX, PDOX had reduced cytotoxicity on LO2 cells and NRK-52E cells.