gsk-2334470 and Pheochromocytoma

gsk-2334470 has been researched along with Pheochromocytoma* in 1 studies

Other Studies

1 other study(ies) available for gsk-2334470 and Pheochromocytoma

Article	Year
PDK1 Inhibitor GSK-470 Exhibits Potent Anticancer Activity in a Pheochromocytoma PC12 Cell Tumor Model via Akt/mTOR Pathway. Anti-cancer agents in medicinal chemistry, 2020, Volume: 20, Issue:7 Phosphoinositide-Dependent Kinase 1 (PDK1) is now widely studied in malignant solid tumors. Researchers have previously revealed that targeting PDK1 is thought of as a promising anticancer treatment strategy. The aim of this study was designed to evaluate the anticancer activity of GSK-470, a novel and highly specific inhibitor of PDK1, in Pheochromocytoma (PCC) tumor model.. PC12 cells were xenografted into nude mice to build PCC tumor model. Animals were treated with GSK-470 vs vehicle. Mean tumor volume was calculated and compared across groups. TUNEL was used to detect apoptosis. The effects of PDK1 inhibitor GSK-470 on activation of the Akt signaling and its downstream Akt/mTOR pathway in xenotransplant tumor tissues were examined by western bolt.. The mean tumor volume in GSK-470 group was significantly less than that in control group. TUNEL results found that cell apoptosis was markedly increased in GSK-470 group compared with the control group. The western bolt analysis showed that the phosphorylation of Akt at threonine 308 was significantly reduced in GSK-470 group. Also, GSK-470 strongly inhibited phosphorylation of mTOR on Ser2448, a marker for mTORC1 activity, as well as phosphorylation of p70S6K, best characterized targets of mTOR.. Our results showed that GSK-470 exhibited potent anticancer activity in PC12 tumor-bearing mice. Also, we found that this effect appeared to be mediated by the inhibition of the Akt/mTOR pathway. The present study once again provides new insights into the therapeutic effects of inhibiting PDK1 in the treatment of malignant PCC. Therefore, we propose that GSK-470 might be an effective therapeutic agent for the treatment of malignant PCC. Topics: Adrenal Gland Neoplasms; Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Indazoles; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Docking Simulation; Molecular Structure; Neoplasms, Experimental; PC12 Cells; Pheochromocytoma; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Rats; Structure-Activity Relationship; TOR Serine-Threonine Kinases	2020

Article

Year

PDK1 Inhibitor GSK-470 Exhibits Potent Anticancer Activity in a Pheochromocytoma PC12 Cell Tumor Model via Akt/mTOR Pathway.

Anti-cancer agents in medicinal chemistry, 2020, Volume: 20, Issue:7

Phosphoinositide-Dependent Kinase 1 (PDK1) is now widely studied in malignant solid tumors. Researchers have previously revealed that targeting PDK1 is thought of as a promising anticancer treatment strategy. The aim of this study was designed to evaluate the anticancer activity of GSK-470, a novel and highly specific inhibitor of PDK1, in Pheochromocytoma (PCC) tumor model.. PC12 cells were xenografted into nude mice to build PCC tumor model. Animals were treated with GSK-470 vs vehicle. Mean tumor volume was calculated and compared across groups. TUNEL was used to detect apoptosis. The effects of PDK1 inhibitor GSK-470 on activation of the Akt signaling and its downstream Akt/mTOR pathway in xenotransplant tumor tissues were examined by western bolt.. The mean tumor volume in GSK-470 group was significantly less than that in control group. TUNEL results found that cell apoptosis was markedly increased in GSK-470 group compared with the control group. The western bolt analysis showed that the phosphorylation of Akt at threonine 308 was significantly reduced in GSK-470 group. Also, GSK-470 strongly inhibited phosphorylation of mTOR on Ser2448, a marker for mTORC1 activity, as well as phosphorylation of p70S6K, best characterized targets of mTOR.. Our results showed that GSK-470 exhibited potent anticancer activity in PC12 tumor-bearing mice. Also, we found that this effect appeared to be mediated by the inhibition of the Akt/mTOR pathway. The present study once again provides new insights into the therapeutic effects of inhibiting PDK1 in the treatment of malignant PCC. Therefore, we propose that GSK-470 might be an effective therapeutic agent for the treatment of malignant PCC.

Topics: Adrenal Gland Neoplasms; Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Indazoles; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Docking Simulation; Molecular Structure; Neoplasms, Experimental; PC12 Cells; Pheochromocytoma; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Rats; Structure-Activity Relationship; TOR Serine-Threonine Kinases

2020