Clinical Pharmacology, Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Surgical Research Laboratories, Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Pharmacogenet Genomics. 2021 Apr 1;31(3):60-67. doi: 10.1097/FPC.0000000000000422.
Chemotherapy-induced hematological toxicities are potentially life-threatening adverse drug reactions that vary between individuals. Recently, JMJD1C has been associated with gemcitabine/carboplatin-induced thrombocytopenia in non-small-cell lung cancer patients, making it a candidate marker for predicting the risk of toxicity. This study investigates if JMJD1C knockdown affects gemcitabine/carboplatin-sensitivity in cell lines.
Lentiviral transduction-mediated shRNA knockdown of JMJD1C in the cell lines K562 and MEG-01 were performed using shRNA#32 and shRNA#33. The knockdown was evaluated using qPCR. Cell proliferation, viability, and gemcitabine/carboplatin-sensitivity were subsequently determined using cell counts, trypan blue, and the MTT assay.
ShRNA#33 resulted in JMJD1C downregulation by 56.24% in K562 and 68.10% in MEG-01. Despite incomplete knockdown, proliferation (reduction of cell numbers by 61-68%, day 7 post-transduction) and viability (reduction by 21-53%, day 7 post-transduction) were impaired in K562 and MEG-01 cells. Moreover, JMJD1C knockdown reduced the gemcitabine IC50-value for K562 cells (P < 0.01) and MEG-01 cells (P < 0.05) compared to scrambled shRNA control transduced cells.
Our results suggest that JMJD1C is essential for proliferation, survival, and viability of K562 and MEG-01 cells. Further, JMJD1C also potentially affects the cells gemcitabine/carboplatin-sensitivity. Although further research is required, the findings show that JMJD1C could have an influential role for gemcitabine/carboplatin-sensitivity.
化疗引起的血液学毒性是潜在的危及生命的药物不良反应，个体之间存在差异。最近，JMJD1C 与非小细胞肺癌患者接受吉西他滨/卡铂治疗引起的血小板减少有关，使其成为预测毒性风险的候选标志物。本研究探讨 JMJD1C 敲低是否会影响细胞系中吉西他滨/卡铂的敏感性。
使用 shRNA#32 和 shRNA#33 通过慢病毒转导介导的 shRNA 敲低 K562 和 MEG-01 细胞系中的 JMJD1C。使用 qPCR 评估敲低效果。随后通过细胞计数、台盼蓝和 MTT 测定法测定细胞增殖、活力和吉西他滨/卡铂敏感性。
shRNA#33 在 K562 中使 JMJD1C 下调 56.24%，在 MEG-01 中下调 68.10%。尽管敲低不完全，但 K562 和 MEG-01 细胞的增殖（转导后第 7 天细胞数量减少 61-68%）和活力（转导后第 7 天减少 21-53%）受损。此外，与转导 scrambled shRNA 对照细胞相比，JMJD1C 敲低降低了 K562 细胞（P<0.01）和 MEG-01 细胞（P<0.05）的吉西他滨 IC50 值。
我们的结果表明，JMJD1C 是 K562 和 MEG-01 细胞增殖、存活和活力所必需的。此外，JMJD1C 还可能影响细胞对吉西他滨/卡铂的敏感性。尽管需要进一步研究，但这些发现表明 JMJD1C 可能对吉西他滨/卡铂的敏感性有影响作用。
