Effect of Hsp90 Inhibitor Ganetespib Combined with Pemetrexed on Lung Adenocarcinoma Cells

Shengqiang YANG; Ping WANG

doi:10.12259/j.issn.2095-610X.S20240705

Volume 45 Issue 7

Jul. 2024

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Shengqiang YANG, Ping WANG. Effect of Hsp90 Inhibitor Ganetespib Combined with Pemetrexed on Lung Adenocarcinoma Cells[J]. Journal of Kunming Medical University, 2024, 45(7): 30-41. doi: 10.12259/j.issn.2095-610X.S20240705

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Shengqiang YANG, Ping WANG. Effect of Hsp90 Inhibitor Ganetespib Combined with Pemetrexed on Lung Adenocarcinoma Cells[J]. Journal of Kunming Medical University, 2024, 45(7): 30-41. doi: 10.12259/j.issn.2095-610X.S20240705

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Effect of Hsp90 Inhibitor Ganetespib Combined with Pemetrexed on Lung Adenocarcinoma Cells

doi: 10.12259/j.issn.2095-610X.S20240705

Shengqiang YANG,
Ping WANG^,

Dept. of Thoracic Surgery，The 2nd Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2024-03-12
Available Online: 2024-06-15
Publish Date: 2024-07-25

Abstract

Abstract

Objective To investigate the effects of Ganetespib and Pemetrexed on the proliferation, apoptosis and related signaling pathways of human lung adenocarcinoma cells in vitro. Methods Human lung adenocarcinoma cells HCC827, H1975, and A549 were divided into groups （Ganetespib group, pemetrexed group, combined treatment group）, and a control group （DMSO 0.2%） was set up. After culturing for 48 hours, the Cell Titer-Glo （CTG） method was used to detect the inhibitory effects of cell proliferation in vitro, and Western blot was used to detect the expression levels of Akt, p-Akt, and Bcl-2 proteins in cells. The apoptosis experiment was used to detect the apoptosis rate, and RNA-seq was used to detect the effects of the two drugs on the transcription level of the HCC827 cell line. Results The inhibitory effects of cell proliferation were as follows: Ganetespib > pemetrexed （P < 0.001）, and the inhibitory effect was enhanced when the two drugs were combined （P < 0.0001）; the apoptosis rate was as follows: Ganetespib > pemetrexed （P < 0.05）, and the apoptosis rate of HCC827 cells increased when the two drugs were combined; the phosphorylation level of Akt protein was lower in the Ganetespib group （P < 0.05）, and the phosphorylation level of Akt protein was higher in the pemetrexed group （P < 0.05）, and the results of the combined treatment group were similar to those of the Ganetespib group, and Bcl-2 protein was only downregulated in A549 cells （P < 0.01）; the two drugs had an effect on the gene transcription level of the HCC827 cell line, with 102 upregulated differentially expressed genes and 27 downregulated genes in the Ganetespib group, 53 upregulated differentially expressed genes and 8 downregulated genes in the pemetrexed group. Conclusion The combination of Ganetespib and pemetrexed can significantly inhibit the proliferation of lung adenocarcinoma cells HCC827, H1975, and A549, induce cell apoptosis. The molecular mechanism may be through the inhibition of lung adenocarcinoma cell proliferation by protein phosphorylation in the PI3K/AKT signaling pathway. The transcriptome of HCC827 cells was affected by the combination therapy. The combined treatment can enhance the inhibition of lung adenocarcinoma cell proliferation to some extent, and the specific mechanism needs further research.
- Lung adenocarcinoma,
- Ganetespib,
- Pemetrexed

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References(36)

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