多细胞营养因子(PTN)对卵巢癌症细胞紫杉醇耐药性的影响

Li Yunfei, L. Huali, Ding Linlin, You Liwei, Zhang Yuqiang, Wang Xingxing, Lin Xueyuan, Yang Liquan
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摘要

卵巢疾病的发病机制与PTN及其受体蛋白酪氨酸磷酸酶受体Z1(PTPRZ1)有关。紫杉醇是治疗癌症的一线药物。随着紫杉醇化疗的增加,紫杉醇阻塞在治疗后期发生的频率较高。通过用PTN处理A2780和SKOV-3细胞,我们发现这两种细胞系的发育得到了增强。向紫杉醇处理的A2780和SKOV-3细胞中加入不同浓度的PTN,MTT结果表明紫杉醇对这两种细胞系的抑制作用减弱。细胞凋亡测定结果表明,PTN可减缓两种细胞系的细胞凋亡率及其浓度依赖性。为了进一步研究PTN对卵巢恶性生长细胞紫杉醇反应性的影响,用sh-PTN-1、sh-PTN-2和sh-NC质粒转染A2780和SKOV-3细胞。PCR和Western Blot结果表明,两种RNA干扰质粒均能抑制A2780和SKOV-3细胞中的PTN。MTT结果显示,紫杉醇对sh-PTN-1转染细胞的抑制作用比对照组扩大。细胞凋亡测定表明,紫杉醇诱导sh-PTN-1质粒A2780和SKOV-3细胞的完全凋亡速度明显加快。综上所述,PTN可增强卵巢癌症细胞对紫杉醇的耐药性,为研究癌症细胞对紫杉酚的耐药性提供了基础,为卵巢癌症治疗提供了新的前景。
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Effects of Pleiotrophin (PTN) on the resistance to paclitaxel in ovarian cancer cells
The pathogenesis of an ovarian disease is connected with PTN and its receptor protein tyrosine phosphatase receptor Z1 (PTPRZ1). Paclitaxel is the first-line drug for the therapy of ovarian cancer. With the increment of paclitaxel chemotherapy, paclitaxel obstruction happens in the late phase of therapy frequently. By treating A2780 and SKOV-3 cells with PTN, we found the development of the two cell lines was enhanced. Different concentrations of PTN were added to A2780 and SKOV-3 cells treated with paclitaxel and the results of MTT showed that the inhibitory effect of paclitaxel on these two cell lines was weakened. The results of apoptosis assays showed that PTN could slow down the rate of apoptosis and its concentration dependence in both cell lines. To further investigate the impact of PTN on the paclitaxel responsiveness of ovarian malignant growth cells, A2780 and SKOV-3 cells were transfected with sh-PTN-1, sh-PTN-2 and sh-NC plasmids. The results of PCR and Western Blot showed that both RNA-interfering plasmids could inhibit PTN in A2780 and SKOV-3 cells. The results of MTT showed that the inhibitory effect of paclitaxel on cells transfected with sh-PTN-1 expanded compared with the benchmark group. Apoptosis assays showed that the complete apoptosis pace of A2780 and SKOV-3 cells with sh-PTN-1 plasmid induced by paclitaxel was accelerated obviously compared with the benchmark group. To summarize, the results suggested that PTN could enhance the resistance to paclitaxel in ovarian cancer cells, which provides a groundwork for studying on drug resistance of cancer cells to paclitaxel and a new perspective for ovarian cancer therapy.
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