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  2. Placenta-specific protein 8 promotes the proliferation of lung adenocarcinoma PC-9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway

Placenta-specific protein 8 promotes the proliferation of lung adenocarcinoma PC-9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway

  • Oncol Lett. 2019 Nov;18(5):5621-5627. doi: 10.3892/ol.2019.10911.
Xiaofei Zeng 1 Qing Liu 2 Yanhui Yang 3 Weikun Jia 1 Shuping Li 1 Dongsheng He 1 Ruidong Ma 1
Affiliations

Affiliations

  • 1 Department of Cardiothoracic Surgery, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China.
  • 2 Department of Cardiothoracic Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China.
  • 3 Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Sichuan 641000, P.R. China.
Abstract

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.

Keywords

Erk1/2; epidermal growth factor receptor tyrosine kinase inhibitor; lung adenocarcinoma; placenta-specific protein 8; proliferation.

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