Zeng Xiaofei, Liu Qing, Yang Yanhui, Jia Weikun, Li Shuping, He Dongsheng, Ma Ruidong
Department of Cardiothoracic Surgery, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China.
Department of Cardiothoracic Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China.
Oncol Lett. 2019 Nov;18(5):5621-5627. doi: 10.3892/ol.2019.10911. Epub 2019 Sep 24.
Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated the effect of PLAC8 on the proliferation of lung adenocarcinoma PC-9 cells and their sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It was found that the inhibition of PLAC8 expression in PC-9 cells resulted in significantly decreased proliferation, whereas overexpression of PLAC8 significantly increased the proliferation (P<0.05) of PC-9 cells. Furthermore, inhibition of PLAC8 expression resulted in decreased activity of the ERK signaling pathway, while PLAC8 overexpression increased activity of this pathway. Inhibition of the ERK signaling pathway with U0126 reversed the effects induced by inhibiting or overexpressing PLAC8 on cell proliferation. In addition, overexpression of PLAC8 significantly decreased the sensitivity of PC-9 cells to gefitinib, and this effect was reversed by U0126. Overall, these results suggest that PLAC8 is involved in the regulation of proliferation of lung adenocarcinoma PC-9 cells and impacts their sensitivity to an EGFR-TKI. Thus, PLAC8 is a potential novel target in lung adenocarcinoma for future studies.
胎盘特异性蛋白8(PLAC8)是一种分子量为12.5 kDa的保守蛋白。该蛋白的具体功能尚未完全阐明,然而,已发现PLAC8在某些类型的癌症(包括结肠癌、胰腺癌和肝癌)中发挥重要的肿瘤调节作用。PLAC8还参与细胞周期、自噬、上皮-间质转化及其他细胞功能的调节,表明其作为一个值得进一步研究的分子靶点的潜力。本研究探讨了PLAC8对肺腺癌PC-9细胞增殖及其对表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)吉非替尼敏感性的影响。研究发现,抑制PC-9细胞中PLAC8的表达会导致增殖显著降低,而PLAC8的过表达则显著增加PC-9细胞的增殖(P<0.05)。此外,抑制PLAC8的表达会导致ERK信号通路活性降低,而PLAC8的过表达则增加该通路的活性。用U0126抑制ERK信号通路可逆转抑制或过表达PLAC8对细胞增殖所诱导的效应。另外,PLAC8的过表达显著降低PC-9细胞对吉非替尼的敏感性,而U0126可逆转这种效应。总体而言,这些结果表明PLAC8参与肺腺癌PC-9细胞增殖的调节并影响其对EGFR-TKI的敏感性。因此,PLAC8是未来肺腺癌研究中一个潜在的新靶点。