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Expression of PI3K/AKT pathway in gastric cancer and its blockade suppresses tumor growth and metastasis.
Int J Immunopathol Pharmacol. 2012 Jul-Sep; 25(3):627-36.IJ

Abstract

Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway plays a crucial role in the formation and progression of many malignancies, and has been shown to be an important therapeutic target for cancer. In the present study, human gastric adenocarcinoma tissues of different grades (N=45) were collected. The protein expression of PI3Kp85α and phosphorylated AKT (p-AKT) was evaluated immunohistochemically in the biopsy samples. PI3K/AKT pathway was blocked by constructed recombinant small hairpin RNA adenovirus vector rAd5-PI3Kp85α (rAd5-P) used to transfect into human gastric cancer SGC-7901cell line. The transfection efficiency of rAd5-P in SGC-7901 cells was observed under fluorescent microscope. The expression of PI3Kp85α, p-AKT, Ki-67 and matrix metallopeptidase-2 (MMP-2) was detected by real-time PCR and Western blot assays. Cell proliferative activities and metastatic capabilities were determined by MTT and Transwell assays. As a consequence, the protein expression of PI3Kp85α and p-AKT was respectively observed in 80.0% and 82.2% gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Targeted blockade of PI3K pathway decreased the expression of PI3Kp85α, p-AKT, Ki-67 and MMP-2, and inhibited the proliferative activities and metastatic capabilities of gastric cancer cells. In conclusion, PI3Kp85α and p-AKT were strongly expressed in gastric adenocarcinoma tissues, and targeted blockade of PI3K pathway may inhibit gastric cancer growth and metastasis through down-regulation of Ki-67 and MMP-2 expression. PI3K/AKT pathway may represent an important therapeutic target for gastric cancer.

Authors+Show Affiliations

Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23058013

Citation

Ye, B, et al. "Expression of PI3K/AKT Pathway in Gastric Cancer and Its Blockade Suppresses Tumor Growth and Metastasis." International Journal of Immunopathology and Pharmacology, vol. 25, no. 3, 2012, pp. 627-36.
Ye B, Jiang LL, Xu HT, et al. Expression of PI3K/AKT pathway in gastric cancer and its blockade suppresses tumor growth and metastasis. Int J Immunopathol Pharmacol. 2012;25(3):627-36.
Ye, B., Jiang, L. L., Xu, H. T., Zhou, D. W., & Li, Z. S. (2012). Expression of PI3K/AKT pathway in gastric cancer and its blockade suppresses tumor growth and metastasis. International Journal of Immunopathology and Pharmacology, 25(3), 627-36.
Ye B, et al. Expression of PI3K/AKT Pathway in Gastric Cancer and Its Blockade Suppresses Tumor Growth and Metastasis. Int J Immunopathol Pharmacol. 2012 Jul-Sep;25(3):627-36. PubMed PMID: 23058013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of PI3K/AKT pathway in gastric cancer and its blockade suppresses tumor growth and metastasis. AU - Ye,B, AU - Jiang,L-L, AU - Xu,H-T, AU - Zhou,D-W, AU - Li,Z-S, PY - 2012/10/13/entrez PY - 2012/10/13/pubmed PY - 2012/12/12/medline SP - 627 EP - 36 JF - International journal of immunopathology and pharmacology JO - Int J Immunopathol Pharmacol VL - 25 IS - 3 N2 - Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway plays a crucial role in the formation and progression of many malignancies, and has been shown to be an important therapeutic target for cancer. In the present study, human gastric adenocarcinoma tissues of different grades (N=45) were collected. The protein expression of PI3Kp85α and phosphorylated AKT (p-AKT) was evaluated immunohistochemically in the biopsy samples. PI3K/AKT pathway was blocked by constructed recombinant small hairpin RNA adenovirus vector rAd5-PI3Kp85α (rAd5-P) used to transfect into human gastric cancer SGC-7901cell line. The transfection efficiency of rAd5-P in SGC-7901 cells was observed under fluorescent microscope. The expression of PI3Kp85α, p-AKT, Ki-67 and matrix metallopeptidase-2 (MMP-2) was detected by real-time PCR and Western blot assays. Cell proliferative activities and metastatic capabilities were determined by MTT and Transwell assays. As a consequence, the protein expression of PI3Kp85α and p-AKT was respectively observed in 80.0% and 82.2% gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Targeted blockade of PI3K pathway decreased the expression of PI3Kp85α, p-AKT, Ki-67 and MMP-2, and inhibited the proliferative activities and metastatic capabilities of gastric cancer cells. In conclusion, PI3Kp85α and p-AKT were strongly expressed in gastric adenocarcinoma tissues, and targeted blockade of PI3K pathway may inhibit gastric cancer growth and metastasis through down-regulation of Ki-67 and MMP-2 expression. PI3K/AKT pathway may represent an important therapeutic target for gastric cancer. SN - 0394-6320 UR - https://www.unboundmedicine.com/medline/citation/23058013/Expression_of_PI3K/AKT_pathway_in_gastric_cancer_and_its_blockade_suppresses_tumor_growth_and_metastasis_ L2 - https://journals.sagepub.com/doi/10.1177/039463201202500309?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -