Effect of inhibition of the adrenomedullin gene on the growth and chemosensitivity of ovarian cancer cells

Chen, Pan; Pang, Xiaoyan; Zhang, Yi; He, Yun-Qin

doi:10.3892/or.2012.1655

Cited by 9 publications

(12 citation statements)

References 10 publications

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“…The ADM-specific short hairpin RNA (shRNA) and no-science shRNA were designed and constructed in our previously study [25]. The oligonucleotide shRNAs based on the small interfering RNA (siRNA) sequences were cloned into pRNA-U6.1/Neo (GeneScript, Piscataway, NJ, USA), respectively.…”

Section: Methodsmentioning

confidence: 99%

The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway

Pang

Shang

Deng

et al. 2013

IJMS

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Tumor-associated macrophages (TAMs) are correlated with poor prognosis in many human cancers; however, the mechanism by which TAMs facilitate ovarian cancer cell migration and invasion remains unknown. This study was aimed to examine the function of adrenomedullin (ADM) in macrophage polarization and their further effects on the migration of ovarian cancer cells. Exogenous ADM antagonist and small interfering RNA (siRNA) specific for ADM expression were treated to macrophages and EOC cell line HO8910, respectively. Then macrophages were cocultured with HO8910 cells without direct contact. Flow cytometry, Western blot and real-time PCR were used to detect macrophage phenotype and cytokine production. The migration ability and cytoskeleton rearrangement of ovarian cancer cells were determined by Transwell migration assay and phalloidin staining. Western blot was performed to evaluate the activity status of signaling molecules in the process of ovarian cancer cell migration. The results showed that ADM induced macrophage phenotype and cytokine production similar to TAMs. Macrophages polarized by ADM promoted the migration and cytoskeleton rearrangement of HO8910 cells. The expression of RhoA and its downstream effector, cofilin, were upregulated in macrophage-induced migration of HO8910 cells. In conclusion, ADM could polarize macrophages similar to TAMs, and then polarized macrophages promote the migration of ovarian cancer cells via activation of RhoA signaling pathway in vitro.

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Section: Methodsmentioning

confidence: 99%

The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway

Pang

Shang

Deng

et al. 2013

IJMS

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“…Tumour cell lines evaluated included small cell lung carcinomas, non-small cell lung carcinomas, breast, nervous system (glioblastoma, neuroblastomas), ovarian, prostate, adrenal, chondrosarcoma, and chronic monocytic leukemia [ 166 ]. These data have been replicated on different tumour cell lines such as pancreatic cell lines (PANC1, L3.6, HPAFII, SU86.86) [ 110 , 116 , 169 ], gliomas [ 170 , 171 ], prostate cancer cell lines [ 162 , 172 – 175 ], ovarian cancer [ 149 , 176 , 177 ], osteosarcoma [ 109 ], renal carcinoma [ 121 , 178 ], multiple myeloma [ 179 ], bladder urothelial cell carcinoma [ 120 ], pituitary adenomas [ 145 ], colorectal cancer [ 119 , 147 , 148 ], breast cancer [ 144 ], endometrial cancer [ 38 ], hepatocellular carcinoma [ 132 ] and others.…”

Section: Introductionmentioning

confidence: 87%

“…As noted above, the presence of AM peptide, as well as AM receptors, has been described in ovarian cancer cells [ 178 ]. Silencing of the AM gene inhibited the proliferation and increased the chemosensitivity of HO8910 cells by downregulation of Bcl-2 and p-ERK, as described for other cancer cell types [ 176 ]. However, other authors have reported that AM effect in ovarian cancer cells is weak as revealed by proliferation assays and cell cycle analysis performed under stressing conditions, such as serum starvation and/or hypoxia [ 149 ].…”

Section: Introductionmentioning

confidence: 97%

“…AM can stimulate cell growth and inhibit apoptosis in a variety of tumour cells, including prostate cancer [ 172 , 174 , 175 ], ovarian cancer [ 149 , 176 ], osteosarcoma [ 109 ], renal carcinoma [ 178 ], bladder carcinoma [ 120 ], breast cancer [ 186 ], colorectal cancer [ 119 , 148 ], gliomas [ 170 ], and hepatocellular carcinoma [ 132 ].…”

Section: Introductionmentioning

confidence: 99%

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Adrenomedullin and tumour microenvironment

et al. 2014

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Adrenomedullin (AM) is a regulatory peptide whose involvement in tumour progression is becoming more relevant with recent studies. AM is produced and secreted by the tumour cells but also by numerous stromal cells including macrophages, mast cells, endothelial cells, and vascular smooth muscle cells. Most cancer patients present high levels of circulating AM and in some cases these higher levels correlate with a worst prognosis. In some cases it has been shown that the high AM levels return to normal following surgical removal of the tumour, thus indicating the tumour as the source of this excessive production of AM. Expression of this peptide is a good investment for the tumour cell since AM acts as an autocrine/paracrine growth factor, prevents apoptosis-mediated cell death, increases tumour cell motility and metastasis, induces angiogenesis, and blocks immunosurveillance by inhibiting the immune system. In addition, AM expression gets rapidly activated by hypoxia through a HIF-1α mediated mechanism, thus characterizing AM as a major survival factor for tumour cells. Accordingly, a number of studies have shown that inhibition of this peptide or its receptors results in a significant reduction in tumour progression. In conclusion, AM is a great target for drug development and new drugs interfering with this system are being developed.

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“…In our previous study, we had constructed short hairpin RNA (shRNA) targeting ADM gene in vitro 31. The oligonucleotide shRNA based on the small interfering (siRNA) sequences were cloned into pRNA-U6.1/Neo (GeneScript, Piscataway, NJ, USA), named pRNA-shADM.…”

Section: Methodsmentioning

confidence: 99%

Adrenomedullin promotes angiogenesis in epithelial ovarian cancer through upregulating hypoxia-inducible factor-1α and vascular endothelial growth factor

Zhang

et al. 2017

Sci Rep

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Adrenomedullin (ADM) is a multi-functional peptide related to many kinds of tumors. This study was aimed to investigate the role of ADM on angiogenesis in epithelial ovarian cancer (EOC) and its possible mechanism. The expressions of ADM, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) and CD34 were examined by immunohistochemistry staining. The relationship among ADM, HIF-1α, VEGF and micro-vessel density (MVD) was assessed in 56 EOC tissues. CAOV3 cells were stably transfected with pcDNA-ADM (plasmid overexpressing ADM gene) or pRNA-shADM (small interfering RNA for ADM gene). Real-time PCR and western blot analysis were performed to detect the expressions of HIF-1α and VEGF. The MTT, transwell migration assay and in vitro tube formation analysis were used to evaluate the proliferation, migration, and tube formation ability of human umbilical vein endothelial cells (HUVECs) which were pretreated with ADM or ADM receptor antagonist ADM22-52. Our findings showed that ADM expression was positively correlated with the expressions of HIF-1α, VEGF or MVD in EOC. ADM upregulated expression of HIF-1α and VEGF in CAOV3 cells. ADM promoted HUVECs proliferation, migration and tube formation. In conclusion, ADM was an upstream molecule of HIF-1α/VEGF and it promoted angiogenesis through upregulating HIF-1α/VEGF in EOC.

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Effect of inhibition of the adrenomedullin gene on the growth and chemosensitivity of ovarian cancer cells

Cited by 9 publications

References 10 publications

The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway

The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway

Adrenomedullin and tumour microenvironment

Adrenomedullin promotes angiogenesis in epithelial ovarian cancer through upregulating hypoxia-inducible factor-1α and vascular endothelial growth factor

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