Cyanidin-3-glucoside suppresses the progression of lung adenocarcinoma by downregulating TP53I3 and inhibiting PI3K/AKT/mTOR pathway.
The aim of this study is to unravel the role of Cyanidin-3-glucoside (C3G) and its potential mechanisms in lung adenocarcinoma (LUAD).
The cell clones, proliferation, apoptosis, migration, and invasion in H1299 and A549 cells were determined by colony formation assay, 5-ethynyl-20 deoxyuridine (EdU) assay, flow cytometry, and transwell assay, respectively. The expression of p53-induced gene 3 (TP53I3) was assessed and the prognostic values of TP53I3 in LUAD via the dataset from the Cancer Genome Atlas (TCGA). In addition, the mRNA and protein expressions were detected by quantitative real-time PCR (qRT-PCR) and western blot.
C3G inhibited the proliferation, migration, and invasion of, and also promoted the apoptosis in H1299 and A549 cells. The database of TCGA showed TP53I3 was highly expressed in LUAD tissues and correlated with the poor prognosis of LUAD patients. Moreover, we also found that C3G inhibited the proliferation, migration and invasion, and promoted apoptosis in H1299 and A549 cells by downregulating TP53I3. Additionally, C3G could inhibit the activation of phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in H1299 and A549 cells by downregulating TP53I3.
This study demonstrated that C3G could inhibit the proliferation, migration and invasion, and also facilitate the apoptosis through downregulating TP53I3 and inhibiting PI3K/AKT/mTOR pathway in LUAD.
Chen X
，Zhang W
，Xu X
《World Journal of Surgical Oncology》
SLC39A5 promotes lung adenocarcinoma cell proliferation by activating PI3K/AKT signaling.
Lung cancer is the most common cancer and the primary cause of cancer-related deaths worldwide. Solute carrier family 39 member 5 (SLC39A5) regulates cellular zinc homeostasis and plays a vital role in several human cancers. However, the clinical significance and biological function of SLC39A5 in lung adenocarcinoma (LUAD) remain unclear. Hence, we sought to elucidate the role of SLC39A5 in LUAD pathophysiology in this study. The expression and clinical significance of SLC39A5 were evaluated using The Cancer Genome Atlas, the Gene Expression Omnibus, and tissue microarray data. We used the Cell Counting Kit-8, flow cytometry, western blotting, and quantitative reverse transcriptase-polymerase chain reaction analyses to determine the function of SLC39A5 in vitro. We also used a mouse xenograft model to evaluate the function of SLC39A5 in vivo. Our results indicate that SLC39A5 was upregulated in LUAD tissues compared with that in adjacent non-tumor lung tissues. SLC39A5 overexpression correlated with poor survival in patients with LUAD. SLC39A5 promoted LUAD cell proliferation by accelerating the G1-to-S phase transition and inhibiting apoptosis. SLC39A5 knockdown inhibited the tumorigenesis of LUAD cells in a nude mouse model of xenograft tumors. SLC39A5 promoted LUAD cell proliferation by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling. SLC39A5 played an oncogenic role in LUAD by activating the PI3K/AKT signaling. Hence, SLC39A5 may serve as a novel prognostic biomarker and potential therapeutic target for LUAD.
Liu Z
，Hu Z
，Cai X
，Liu S
... -
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TM6SF1 suppresses the progression of lung adenocarcinoma and M2 macrophage polarization by inactivating the PI3K/AKT/mtor pathway.
Transmembrane 6 superfamily 1 (TM6SF1) is lowly expressed in lung adenocarcinoma (LUAD), but the function and mechanisms of TM6SF1 remain unclear. Thus, we attempt to explore the function of TM6SF1 and its underlying mechanisms in LUAD. qRT-PCR was used for detecting TM6SF1 mRNA expression. Immunohistochemistry staining was used for detecting the expression of MMP-2, TM6SF1, Ki67, MMP-9, and CD163 proteins. E-cadherin, p-PI3K, Vimentin, AKT, N-cadherin, PI3K, p-AKT, mTOR, p-mTOR, and marker proteins of M2 macrophages were evaluated using Western blot. CD206 protein expression was examined via immunofluorescence. The IL-10 concentration was measured via enzyme-linked immunosorbent assay (ELISA). Using CCK-8, colony formation and transwell assays, cell proliferation, migration, and invasion were assessed. A549 cells were injected into the mice's flank for establishing a mouse tumor model and into the tail vein for establishing the lung metastasis model. HE staining was performed to detect pathological changes in lung tissues. Decreased TM6SF1 expression was found in LUAD tissues and cells. TM6SF1 overexpression inhibited cell viability, proliferation, invasion, migration, EMT, and polarization of M2 macrophages in LUAD cells, along with tumor growth and metastasis in xenograft mice. Bioinformatics analysis demonstrated that TM6SF1 was correlated with the tumor microenvironment. TM6SF1 overexpression reduced expression levels of p-mTOR, p-PI3K, p-AKT, mTOR, and AKT. TM6SF1-caused inhibition of proliferation, migration, invasion and EMT, as M2 macrophage polarization was reversed by the PI3K activator in LUAD cells. TM6SF1 inactivated the PI3K/AKT/mTOR pathway to suppress LUAD malignancy and polarization of M2 macrophages, providing insight for developing new LUAD treatments.
Huang S
，Zhao H
，Lou X
，Chen D
，Shi C
，Ren Z
... -
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ResearchGate
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钛学术
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