Department of Chinese Medicine, Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan.
School of Traditional Chinese Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan.
Int J Mol Sci. 2022 Jun 3;23(11):6290. doi: 10.3390/ijms23116290.
Chemotherapy-induced thrombocytopenia (CIT) is a common complication when treating malignancies with cytotoxic agents wherein carboplatin is one of the most typical agents causing CIT. Janus kinase 2 (JAK2) is one of the critical enzymes to megakaryocyte proliferation and differentiation. However, the role of the JAK2 in CIT remains unclear. In this study, we used both carboplatin-induced CIT mice and MEG-01 cell line to examine the expression of JAK2 and signal transducer and activator of transcription 3 (STAT3) pathway. Under CIT, the expression of JAK2 was significantly reduced in vivo and in vitro. More surprisingly, the JAK2/STAT3 pathway remained inactivated even when thrombopoietin (TPO) was administered. On the other hand, carboplatin could cause prominent S phase cell cycle arrest and markedly increased apoptosis in MEG-01 cells. These results showed that the thrombopoiesis might be interfered through the downregulation of JAK2/STAT3 pathway by carboplatin in CIT, and the fact that exogenous TPO supplement cannot reactivate this pathway.
化疗诱导的血小板减少症（CIT）是使用细胞毒性药物治疗恶性肿瘤时的一种常见并发症，其中卡铂是导致 CIT 的最典型药物之一。Janus 激酶 2（JAK2）是巨核细胞增殖和分化的关键酶之一。然而，JAK2 在 CIT 中的作用尚不清楚。在这项研究中，我们使用卡铂诱导的 CIT 小鼠和 MEG-01 细胞系来研究 JAK2 和信号转导和转录激活因子 3（STAT3）通路的表达。在 CIT 下，JAK2 的表达在体内和体外均显著降低。更令人惊讶的是，即使给予血小板生成素（TPO），JAK2/STAT3 通路仍保持失活。另一方面，卡铂可导致 MEG-01 细胞中明显的 S 期细胞周期停滞和显著增加的细胞凋亡。这些结果表明，CIT 中卡铂通过下调 JAK2/STAT3 通路可能干扰了血小板生成，并且外源性 TPO 补充不能重新激活该通路。
