Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression

Chen, Xiaowan; Li, Chenli; He, Tiantian; Mao, Jiating; Li, Chunmei; Lyu, Jianxin; Meng, Qing H.

doi:10.1080/15384047.2016.1156273

Cited by 48 publications

(69 citation statements)

References 32 publications

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“…Recent studies have suggested that these hypoglycemic drugs, such as metformin, decrease the prostate specific antigen (PSA) level, epithelial-mesenchymal transition (EMT) and proliferation of PCa [48][49][50]. These studies confirm our present study showing that hyperglycemia drives PCa progressions.…”

Section: Discussionsupporting

confidence: 92%

High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells

Huang¹,

Lin²,

Lin³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hyperglycemia has been shown to increase the incidence and metastasis in various types of cancers. However, the correlation between hyperglycemia and lymphatic metastasis in prostate cancer (PCa) remains unclear. Our previous study demonstrated that lysophosphatidic acid (LPA) enhances vascular endothelial growth factor-C (VEGF-C) expression, a lymphangiogenic factor, through activating it receptors LPA_1/3 in prostate cancer (PCa) cells. Moreover, hyperglycemia up-regulates autotaxin (ATX) expression, a LPA-generating enzyme. Therefore, we propose that high glucose promotes VEGF-C expression through LPA signaling in PCa cells. Methods: Pharmacological inhibitors and siRNAs were utilized to investigate the molecular mechanism of high glucose-induced VEGF-C expression. Real-time PCR and Western blot were used to determine the mRNA and protein expressions, respectively. Cellular bioenergetics analysis was performed to determine the glycolysis levels. Results: We demonstrated that the expressions of VEGF-C, ATX, and calreticulin were increased upon high glucose treatments in PC-3 cells. Moreover, high glucose-induced VEGF-C expression was mediated through the LPA_1/3, PLC, Akt, ROS and LEDGF-dependent pathways. Additionally, high glucose enhanced the aerobic glycolysis via LPA_1/3. Conclusion: These results indicated that hyperglycemia leads to LPA synthesis, and subsequent promoting pathological consequence of PCa. These novel findings could potentially provide new strategies for PCa treatments.

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Section: Discussionsupporting

confidence: 92%

High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells

Huang¹,

Lin²,

Lin³

et al. 2018

Cell Physiol Biochem

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“…Men with diabetes have lower circulating testosterone concentrations, and decreased testosterone may reduce the risk of prostate cancer . Additionally, antidiabetic drugs, such as metformin, can directly influence the prostate cancer growth by inhibiting the proliferation, migration and invasion of the cancer cells . In co‐twin control analyses, the association of diabetes with prostate cancer became stronger suggesting that some familial factors or genes may partially contribute to the diabetes–cancer association, but cannot fully account for it.…”

Section: Discussionmentioning

confidence: 99%

“…46,47 Additionally, antidiabetic drugs, such as metformin, can directly influence the prostate cancer growth by inhibiting the proliferation, migration and invasion of the cancer cells. 48 In co-twin control analyses, the association of diabetes with prostate cancer became stronger suggesting that some familial factors or genes may partially contribute to the diabetes-cancer association, but cannot fully account for it. Further studies are needed to identify which are the familial factors or genes that play a role in such an association.…”

Section: Discussionmentioning

confidence: 99%

Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study

Bao

Pedersen

Yang

et al. 2018

Intl Journal of Cancer

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The association between diabetes and cancer risk remains controversial. Hence, we examined whether midlife diabetes is related to the risk of cancer in late-life, and whether genetic and early-life environmental factors play a role in this association. This study included 25,154 twin individuals born in 1958 or earlier from the Swedish Twin Registry. Information on cancer diagnosis in late life (aged ≥ 65) during 1998-2014, was derived from the National Patient and Cancer Registries. Diabetes was ascertained based on self- or informant-reported history, patient registry and antidiabetic medication use. Midlife diabetes was defined when diabetes was diagnosed before 65 years. Data were analyzed following two strategies: (i) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models, and (ii) co-twin control analysis for cancer-discordant twin pairs using conditional logistic regression. Overall, 1,766 (7.0%) had midlife diabetes and 5,293 (21.0%) had cancer in late-life. In multiadjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95-37.67) for pharynx cancer, 5.78 (1.72-19.40) for small intestine cancer, 2.37 (1.14-4.91) for liver cancer and 0.48 (0.35-0.67) for prostate cancer. In people with diabetes, diabetes duration was dose-dependently associated with cancer risk. In conditional logistic regression analysis of 176 prostate cancer-discordant twin pairs, the association between midlife diabetes and prostate cancer in later life became stronger. Midlife diabetes increases the risk of pharynx, small intestine and liver cancers, but reduces prostate cancer risk in late life. Genetic and early-life environmental factors may partially contribute to the diabetes-prostate cancer association.

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“…Cell apoptosis was detected using the Annexin V-APC Apoptosis Detection kit (KeyGEN Biotech, Nanjing, China) as described in our previous studies and others [41,42,43,44]. Allophycocyanin (APC) is an accessory photosynthetic pigment found in blue-green algae.…”

Section: Methodsmentioning

confidence: 99%

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

Chen

Fang

Zhang

et al. 2017

IJMS

Self Cite

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GlyoxalaseI (GLOI) is an enzyme that catalyzes methylglyoxal metabolism. Overexpression of GLOI has been documented in numerous tumor tissues, including colorectal cancer (CRC). The antitumor effects of GLOI depletion have been demonstrated in some types of cancer, but its role in CRC and the mechanisms underlying this activity remain largely unknown. Our purpose was to investigate the antitumor effects of depleted GLOI on CRC in vitro and in vivo. RNA interference was used to deplete GLOI activity in four CRC cell lines. The cells’ proliferation, apoptosis, migration, and invasion were assessed by using the Cell Counting Kit-8, plate colony formation assay, flow cytometry, and transwell assays. Protein and mRNA levels were analyzed by western blot and quantitative real-time PCR (qRT-PCR), respectively. The antitumor effect of GLOI depletion in vivo was investigated in a SW620 xenograft tumor model in BALB/c nude mice. Our results show that GLOI is over-expressed in the CRC cell lines. GLOI depletion inhibited the proliferation, colony formation, migration, and invasion and induced apoptosis of all CRC cells compared with the controls. The levels of signal transducer and activator of transcription 1 (STAT1), p53, and Bcl-2 assaciated X protein (Bax) were upregulated by GLOI depletion, while cellular homologue of avian myelocytomatosis virus oncogene (c-Myc) and B cell lymphoma/lewkmia-2 (Bcl-2) were downregulated. Moreover, the growth of SW620-induced CRC tumors in BALB/c nude mice was significantly attenuated by GLOI depletion. The expression levels of STAT1, p53, and Bax were increased and those of c-Myc and Bcl-2 were decreased in the GLOI-depleted tumors. Our findings demonstrate that GLOI depletion has an antitumor effect through the STAT1 or p53 signaling pathways in CRC, suggesting that GLOI is a potential therapeutic target.

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Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression

Cited by 48 publications

References 32 publications

High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells

High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells

Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

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