Morphine Suppresses Lung Cancer Cell Proliferation Through the Interaction with Opioid Growth Factor Receptor

88 Background: Mammalian target of rapamycin (mTOR) is a downstream regulatory protein of the PI3K/Akt signal transduction pathway. This is a common pathway for a several cell surface receptors including IGFR (Insulin-like Growth Factor Receptor) and EGFR (Epidermal Growth Factor Receptor). The activation of these receptors through PI3K/Akt pathway is essential in cell proliferation, angiogenesis, and anti-apoptosis process. The upregulation of PI3K could be a mechanism of resistance of mTOR inhibitors. Docetaxel (D) is commonly used in the treatment of lung cancer. We demonstrated previously that the sequence of D followed by mTOR inhibitor temsirolimus (T) in lung cancer cell lines (LCCL) had synergistic effect in suppressing cell proliferation compared with T→D. The exact mechanism of this effect is unknown. We studied the expression of mTOR and PI3K in these cell lines treated in different time points to investigate the activity of this pathway when using these sequences of drug treatment. Methods: Adenocarcinoma LCCL H2122 and H1437 were plated and exposed to temsirolimus 1000nM and docetaxel 100nM. The cell viability was measured by optical density (OD) at 24, 48, and 72h. We tested effect of drugs D and T alone as well as the sequence of D treated for 24h followed by addition of T and the reverse in both LCCL. We then prepared cell lysate at 24h, 48h, and 72h time points and studied the expression of phospho mTOR (pmTOR) and PI3K by western blot using antibody obtained from cell signaling. Results: The use of T alone increased the expression of PI3K in both H2122 and H1437 cell lines at 48h time point. The use of D had a variable response: absent in H1437 and present in H2122 at 48 H. The sequence of D→T suppressed the expression of pmTOR and PI3K at 48 and 72 h compared with the opposite sequence of T→D. Conclusions: The combination of D → T is synergistic in suppression of pmTOR and inhibited the overactivation of upstream PI3K in both LCCL compared with opposite sequence. Therefore, the sequential treatment of D followed by T is able to overcome the PI3K overactivation mechanism of resistance in lung cancer cell line when treated with T. This would have implications in the use of these agents in treatment of lung cancer.

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Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem cells

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmq118 ◽

2010 ◽

Vol 43 (2) ◽

pp. 143-148 ◽

Cited By ~ 29

Author(s):

L. Li ◽

H. Tian ◽

Z. Chen ◽

W. Yue ◽

S. Li ◽

...

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Cell Proliferation ◽

Mesenchymal Stem Cells ◽

Cancer Cell ◽

Human Mesenchymal Stem Cells ◽

Cancer Cell Proliferation ◽

Lung Cancer Cell

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Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1

Bioscience Reports ◽

10.1042/bsr20193309 ◽

2020 ◽

Vol 40 (1) ◽

Cited By ~ 5

Author(s):

Yafeng Fan ◽

Hongxia Li ◽

Zhongping Yu ◽

Wen Dong ◽

Xiaoyan Cui ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cancer Cell ◽

Small Cell ◽

Cancer Cell Proliferation ◽

Lung Cancer Cell ◽

Small Cell Lung ◽

Non Coding Rna ◽

Long Non Coding Rna

Abstract Long non-coding RNA (lncRNA) FYVE, RhoGEF and PH domain containing 5 antisense RNA 1 (FGD5-AS1) has been reported as an oncogene in colorectal cancer, promoting its tumorgenesis. The present paper focused on searching the potential function of FGD5-AS1 in non-small cell lung carcinoma (NSCLC). There are connections between the expression of lncRNA FGD5-AS1 and human NSCLC tumor growth and progression. Also, the relationships between FGD5-AS1, hsa-miR-107 and mRNA fibroblast growth factor receptor like 1 (FGFRL1) are going to test their interaction in NSCLC cell lines, which may cause a series of biological behaviors of NSCLC cells. qRT-PCR analysis was conducted to test the expression of RNAs in different situation. CCK-8 experiment and clone formation assay were performed to assess proliferation of NSCLC cells. Also, connection between FGD5-AS1 and hsa-miR-107 were investigated by luciferase reporter assay and RNA pull-down assay. Rescue experiments were performed to verify the modulating relationship between FGD5-AS1, hsa-miR-107 and FGFRL1. High-level expression of FGD5-AS1 was found in NSCLC. FGD5-AS1 may promote the proliferation of NSCLC cells. Also, the combination between hsa-miR-107, FGD5-AS1 and NSCLC have been proved, which means they can play an interaction function in NSCLC cells. Thence, we concluded that lncRNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1.

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