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GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo.

Zhou X, Shen F, Ma P, Hui H, Pei S, Chen M, Wang Z, Zhou W, Jin B - Mol Med Rep (2015)

Bottom Line: Its anti-proliferative activity has been demonstrated in various tumor cell lines.The GSK1838705A‑treated cells exhibited reduced migratory activity in response to chemoattractants.The present study further demonstrated the antitumor activity of GSK1838705A in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.

ABSTRACT
Glioma is a type of primary malignant tumor of the central nervous system in humans. At present, standard treatment involves surgical resection, followed by radiation therapy and chemotherapy. However, the prognosis is poor and the long‑term survival rate remains low. An improved understanding of the molecular basis for glioma tumorigenesis is in urgently required. The pro‑survival effect of the insulin‑like growth factor (IGF) signaling pathway has been implicated in progression of the glioma disease state. GSK1838705A is a novel, small molecule kinase inhibitor of IGF‑IR, which inhibits IGF signal transduction and downstream target activation. Its anti-proliferative activity has been demonstrated in various tumor cell lines. The present study investigated the potential use of GSK1838705A for the treatment of glioma. Human U87MG glioma cells were used to examine the inhibitory activity of GSK1838705A in cell proliferation, migration and apoptosis. The antitumor activity of GSK1838705A was assessed in a xenograft mouse model. GSK1838705A inhibited the growth and induced the apoptosis of the U87MG glioma cells in a dose‑dependent manner. The GSK1838705A‑treated cells exhibited reduced migratory activity in response to chemoattractants. The present study further demonstrated the antitumor activity of GSK1838705A in vivo. The administration of GSK1838705A significantly inhibited the growth of glioma tumors by inducing the apoptosis of tumor cells. These results suggested that targeting IGF signaling with GSK1838705A may be a promising therapeutic strategy for the treatment of patients with glioma.

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GSK1838705A reduces glioma cell viability. (A) U87MG cells were treated with DMSO or GSK1838705A (1.56–100 µM) for 72 h, followed by measurement of cell viability. The viability of the cells treated with DMSO was set to 100%. (B) U87MG cells were treated with 20 µM GSK1838705A for 24, 48 or 72 h, followed by measurement of cell viability (P<0.05, 48 and 72 vs. 24 h). The data are expressed as the mean ± standard deviation. DMSO, dimethyl sulfoxide.
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f1-mmr-12-04-5641: GSK1838705A reduces glioma cell viability. (A) U87MG cells were treated with DMSO or GSK1838705A (1.56–100 µM) for 72 h, followed by measurement of cell viability. The viability of the cells treated with DMSO was set to 100%. (B) U87MG cells were treated with 20 µM GSK1838705A for 24, 48 or 72 h, followed by measurement of cell viability (P<0.05, 48 and 72 vs. 24 h). The data are expressed as the mean ± standard deviation. DMSO, dimethyl sulfoxide.

Mentions: Cellular proliferation is regulated by the cooperative action of various growth stimulatory and inhibitory signals. IGF signaling favors cell survival by activating downstream signaling transduction cascades, including the Ras, MAPK, PI3K and AKT pathways (8,20). To determine whether the suppression of IGF signaling affected cells proliferation in the present study, the U87MG glioma cells were treated with different concentrations of GSK1838705A for 72 h and the cell viability was measured. A dose-dependent inhibition of glioma cell viability was observed following treatment with GSK1838705A (Fig. 1A). To determine the onset of drug action, the U87MG cells were treated with GSK1838705A (20 µM) for 24, 48 or 72 h, followed by the measurement of cell viability. The results indicated an early onset for the inhibitory effect of GSK1838705A, which was observed 24 h following treatment (Fig. 1B).


GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo.

Zhou X, Shen F, Ma P, Hui H, Pei S, Chen M, Wang Z, Zhou W, Jin B - Mol Med Rep (2015)

GSK1838705A reduces glioma cell viability. (A) U87MG cells were treated with DMSO or GSK1838705A (1.56–100 µM) for 72 h, followed by measurement of cell viability. The viability of the cells treated with DMSO was set to 100%. (B) U87MG cells were treated with 20 µM GSK1838705A for 24, 48 or 72 h, followed by measurement of cell viability (P<0.05, 48 and 72 vs. 24 h). The data are expressed as the mean ± standard deviation. DMSO, dimethyl sulfoxide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581800&req=5

f1-mmr-12-04-5641: GSK1838705A reduces glioma cell viability. (A) U87MG cells were treated with DMSO or GSK1838705A (1.56–100 µM) for 72 h, followed by measurement of cell viability. The viability of the cells treated with DMSO was set to 100%. (B) U87MG cells were treated with 20 µM GSK1838705A for 24, 48 or 72 h, followed by measurement of cell viability (P<0.05, 48 and 72 vs. 24 h). The data are expressed as the mean ± standard deviation. DMSO, dimethyl sulfoxide.
Mentions: Cellular proliferation is regulated by the cooperative action of various growth stimulatory and inhibitory signals. IGF signaling favors cell survival by activating downstream signaling transduction cascades, including the Ras, MAPK, PI3K and AKT pathways (8,20). To determine whether the suppression of IGF signaling affected cells proliferation in the present study, the U87MG glioma cells were treated with different concentrations of GSK1838705A for 72 h and the cell viability was measured. A dose-dependent inhibition of glioma cell viability was observed following treatment with GSK1838705A (Fig. 1A). To determine the onset of drug action, the U87MG cells were treated with GSK1838705A (20 µM) for 24, 48 or 72 h, followed by the measurement of cell viability. The results indicated an early onset for the inhibitory effect of GSK1838705A, which was observed 24 h following treatment (Fig. 1B).

Bottom Line: Its anti-proliferative activity has been demonstrated in various tumor cell lines.The GSK1838705A‑treated cells exhibited reduced migratory activity in response to chemoattractants.The present study further demonstrated the antitumor activity of GSK1838705A in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.

ABSTRACT
Glioma is a type of primary malignant tumor of the central nervous system in humans. At present, standard treatment involves surgical resection, followed by radiation therapy and chemotherapy. However, the prognosis is poor and the long‑term survival rate remains low. An improved understanding of the molecular basis for glioma tumorigenesis is in urgently required. The pro‑survival effect of the insulin‑like growth factor (IGF) signaling pathway has been implicated in progression of the glioma disease state. GSK1838705A is a novel, small molecule kinase inhibitor of IGF‑IR, which inhibits IGF signal transduction and downstream target activation. Its anti-proliferative activity has been demonstrated in various tumor cell lines. The present study investigated the potential use of GSK1838705A for the treatment of glioma. Human U87MG glioma cells were used to examine the inhibitory activity of GSK1838705A in cell proliferation, migration and apoptosis. The antitumor activity of GSK1838705A was assessed in a xenograft mouse model. GSK1838705A inhibited the growth and induced the apoptosis of the U87MG glioma cells in a dose‑dependent manner. The GSK1838705A‑treated cells exhibited reduced migratory activity in response to chemoattractants. The present study further demonstrated the antitumor activity of GSK1838705A in vivo. The administration of GSK1838705A significantly inhibited the growth of glioma tumors by inducing the apoptosis of tumor cells. These results suggested that targeting IGF signaling with GSK1838705A may be a promising therapeutic strategy for the treatment of patients with glioma.

Show MeSH
Related in: MedlinePlus