Neoplasma Vol.71, No.6, p.571–580, 2024
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| Title: Disruption of lipid raft reverses drug resistance in colorectal cancer cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B pathway and P-glycoprotein |
| Author: Jing Chen, Wei Zheng, Qian Li, RanRan Xu, TingTing Bai, Chao Pan |
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Abstract: Regarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental results indicated. However, the exact mechanism underlying this pathway remains unclear. PI3K inhibitor and activator were added separately to clarify the role of the PI3K pathway in reversing drug resistance. The results showed decreased resistance after inhibiting PI3K activity. Furthermore, the reduced resistance due to flotillin knockdown was restored after adding the PI3K activator. Additional results showed no changes in PI3K molecules. However, p-AKT expression was downregulated. Further results suggested that the phosphatidylinositol (3,4,5)-trisphosphate/phosphatidylinositol 4,5-bisphosphate (PIP3/PIP2) ratio was downregulated, whereas the phosphatase and tensin homolog (PTEN) expression was upregulated. In addition, we also found that P-gp activity inhibition resulted in increased adriamycin accumulation and reversal of resistance, and flotillin knockdown was accompanied by a downregulation of P-gp expression in CRC cells. In conclusion, our study demonstrated that flotillin knockdown could reverse drug resistance in CRC cells by downregulating the PTEN/PI3K/AKT pathway and P-gp.
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| Keywords: colorectal cancer; drug resistance; lipid rafts; PI3K/AKT pathway; P-glycoprotein |
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| Year: 2024, Volume: 71, Issue: 6 |
Page From: 571, Page To: 580 |
doi:10.4149/neo_2024_240422N179
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