GOLPH3 Overexpression is Closely Correlated with Poor Prognosis in Human Non-Small Cell Lung Cancer and Mediates its Metastasis Through Upregulating MMP-2 and MMP-9

Background/Aims: α-mangostin has anti-carcinogenic effects against several cancers. We investigated the molecular mechanism of this compound on the metastasis of human renal carcinoma cells. Methods: Cell viability was measured using the MTT assay, and cell cycle distribution using flow cytometry. A Matrigel-based assay was used to measure in vitro cell migration and invasion. MAPK-related proteins and matrix metalloproteinase (MMP)-9 and MMP-2 expression were measured by western blotting, and MMP2/-9 activities were determined by gelatin zymography. RT-qPCR and a luciferase assay were used to examine the transcriptional activity of MMP-9. Results: α-mangostin inhibited the migration and invasion of RCC cells in a dose-dependent manner, but had no evident cytotoxic effects. Treatment of 786-O cells with α-mangostin inhibited activation of MEK and ERK. Treatment with a specific MEK inhibitor (U0126) enhanced the inhibitory effects of α-mangostin on cell migration and invasion, and the phosphorylation of ERK and MEK. Moreover, α-mangostin inhibited the expression of the MMP-9 mRNA levels as well as the activity of MMP-9 promoter, and these suppressive effects were further enhanced by U0126. Conclusions: Our results suggest that α-mangostin suppresses cell migration and invasion via MEK/ERK/MMP9 pathway, and might be a promising anti-metastatic agent against human renal cell carcinoma.

show abstract

“…The medium was subjected to SDS-PAGE in an 8% polyacrylamide gel copolymerized with 0.08% gelatin, as previously reported [22]. …”

Section: Methodsmentioning

confidence: 99%

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

Chen

Hsieh

Lin

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…MMP9 is a member of MMP family, and is secreted by various cancer cells to break down extracellular matrix [23][24][25]. Overexpression of MMP9 has been reported to facilitate metastatic spread of different cancer cells and appears to be an important molecule to directly promote NSCLC metastasis.…”

Section: Introductionmentioning

confidence: 99%

Placental Growth Factor Promotes Metastases of Non-Small Cell Lung Cancer Through MMP9

Zhang¹,

Zhang²,

Lou³

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Neovascularization and invasion coordinate cancer metastases in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms are poorly understood. Recently, a substantial role of placental growth factor (PLGF) in cancer cell invasion has been acknowledged in several types of cancer, whereas a possible involvement of PLGF in the metastases of NSCLC has not been studied. Methods: Here, we analyzed the levels of PLGF and matrix metalloproteinase 9 (MMP9) in NSCLC specimens. We modified either PLGF or MMP9 levels in a NSCLC cell line A549, and examined the effects on the levels of MMP9 and PLGF. The cell invasiveness was quantified in a transwell cell migration assay. Pathway inhibitors were applied to determine the molecular mechanisms underlying the control of MMP9 by PLGF. Results: We found that PLGF and MMP9 levels both significantly increased in the NSCLC specimens and were strongly correlated. Overexpression of PLGF in NSCLC cells increased the levels of MMP9 and cell invasiveness, while inhibition of PLGF in NSCLC cells decreased the levels of MMP9 and cell invasiveness. However, modification of MMP9 levels in NSCLC cells did not alter the levels of PLGF. These data suggest that PLGF may regulate MMP9 in NSCLC cells, but not vice versa. Moreover, inhibition of MMP9 in PLGF-overexpressing NSCLC cells abolished the effects of PLGF on cell invasiveness, suggesting that PLGF increases cell invasion via MMP9. Furthermore, suppression of MAPK-p38, but not suppression of either MAPK-p42/p44, or PI3k, or JNK signaling, substantially abolished the effect of PLGF on MMP9, suggesting that PLGF may activate MMP9 via MAPK-p38 signaling pathway. Conclusion: PLGF-stimulated cancer invasion may be mediated through its effects on MMP9 activation in NSCLC cells.

show abstract

“…Enhanced expression and upgraded activity of MMP-2 and -9 resulted in degradation of extracellular matrix and destruction of basilar membrane, which facilitated the migration of cancer cells (26,27). On the contrary, restricted expression of MMP-2 and -9 in cancer cells leads to a better prognosis (28)(29)(30). The results from the present study showed that exposure of NSCLC H520 cells to phloretin led to decreased invasion and migratory ability.…”

Section: Discussionmentioning

confidence: 51%

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases

Wang

Nan

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases and the prognosis of NSCLC patients is unsatisfactory since 5-year survival rate of NSCLC is still as low as 11%. Natural compounds derived from plants with few or no side effects have been recognized as alternative or auxiliary cure for cancer patients. Phloretin is such an agent possessing various pharmacological activities; however, there is scarce information on its anticancer effects on NSCLC. It was evaluated and confirmed, in the present study, that phloretin inhibited proliferation and induced apoptosis in A549, Calu-1, H838 and H520 cells in a dosedependent manner, phloretin also suppressed the invasion and migration of NSCLC cells. We further confirmed that phloretin dose-dependently suppressed the expression of Bcl-2, increased the protein expression of cleaved-caspase-3 and -9, and deregulated the expression of matrix metalloproteinases (MMP)-2 and -9 on gene and protein levels. Besides, evaluations revealed that phloretin enhanced the anticancer effects of cisplatin on inhibition of proliferation and induction of apoptosis in NSCLC cells. Moreover, phloretin facilitated the effects of cisplatin on deregulation of Bcl-2, MMP-2 and -9, and upregulation of cleaved-caspase-3 and -9. In conclusion, the present study demonstrated that phloretin possessed anticancer effects and enhanced the anticancer effects of cisplatin on NSCLC cell lines by suppressing proliferation, inducing apoptosis and inhibiting invasion and migration of the cells through regulating apoptotic pathways and MMPs. IntroductionLung cancer is the most frequent reason for cancer related death and non-small cell lung cancer (NSCLC) accounts for ~80-85% of all lung cancer cases (1). Although there has been notable progression in combination chemotherapy and surgical techniques, the prognosis of NSCLC patients is still unsatisfactory since 5-year survival rate of NSCLC with all stages and histological types is as low as 11% (2). Besides the prolonged life time, the survival quality of NSCLC patients should also be taken care of, while the high toxicity of anticancer drugs adopted in clinical first line to normal tissues and cells is an impassable barrier for cancer therapy and a heavy burden for patients to bear. It would be better if there were some methods that could improve the clinical therapy effects and relieve the pain of the patients.Agents derived from various plants with few or no side effects have been recognized as potential alternative or auxiliary cure for cancer patients. Flavonoids, one major class of polyphenols, are well known for their antioxidant activity by eliminating reactive oxygen species (3) and chelating metal atoms (4,5). There is also substantial research suggesting that flavonoids have anticancer effects (6). Phloretin [3-(4-hydroxyphenyl)-1-(2,4,5-trihydroxyphenyl)] is one of the major phenolic flavonoid glucosides (structure showed in Fig. 1) found in apples and other plants, such as Pieris japonica, Hoveniae Lignum and...

show abstract

GOLPH3 Overexpression is Closely Correlated with Poor Prognosis in Human Non-Small Cell Lung Cancer and Mediates its Metastasis Through Upregulating MMP-2 and MMP-9

Cited by 57 publications

References 26 publications

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

Placental Growth Factor Promotes Metastases of Non-Small Cell Lung Cancer Through MMP9

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases

Contact Info

Product

Resources

About