PI3K/AKT signaling pathway as a critical regulator of Cisplatin response in tumor cells

Abstract

Chemotherapy is one of the main therapeutic modalities for cancer patients. Cisplatin (CDDP), as one of the first-line drugs, is of great importance in the chemotherapy of various tumors. However, a significant percentage of cancer patients are resistant to CDDP treatment. Due to the CDDP side effects on normal tissues, the diagnosis of CDDP resistance is required to suggest the most efficient therapeutic strategies for cancer patients. Several molecular mechanisms and signaling pathways are associated with CDDP response. The PI3K/AKT signaling pathway has a pivotal role in the transmission of extracellular signals into the cells to regulate various pathophysiological processes such as cell proliferation, migration, and drug resistance. In the present review, we summarized all of the studies which have been reported on the role of PI3K/AKT pathway in regulation of CDDP response. It was shown that the PI3K/AKT pathway is mainly involved in CDDP response in lung, ovarian, and gastrointestinal cancers. It was also observed that the non-coding RNAs have a key role in CDDP response by regulation of PI3K/AKT pathway. This review paves the way for suggesting a PI3K/AKT-related panel marker for the prediction of CDDP response in different cancer patients.

β‐elemene enhances cisplatin sensitivity of non‐small cell lung cancer cells via the miR‐17‐5p/STAT3 axis

“…Considering miR-17-5p and STAT3 pathway are closely associated with chemoresistance of cancer cells (Chatterjee et al, 2014;Jiang et al, 2014;Laurino et al, 2023;Ma et al, 2023;Sun et al, 2019;Yang et al, 2023;Wang & Ji, 2018), and in this study we observe that β-elemene upregulates the expression of miR-17-5p and represses the expression of STAT3, we conclude that β-elemene sensitizes NSCLC cells to cisplatin via modulating miR-17-5p/STAT3 axis, and this is a different mechanism compared with the previous report (Yao et al, 2014). It should be emphasized, cancer cells' resistance to Platinum chemotherapeutic drugs is caused by multiple mechanisms, and modulated by various signal pathways, such as the activation of PI3K/Akt pathway, pentose phosphate pathway, abnormal epigenetic modifications et al (Giacomini et al, 2020;Navaei et al, 2022;Zhang et al, 2014). The other mechanisms by which β-elemene sensitizes NSCLC cells to chemotherapeutics are far from being fully clarified.…”

“…It should be emphasized, cancer cells' resistance to Platinum chemotherapeutic drugs is caused by multiple mechanisms, and modulated by various signal pathways, such as the activation of PI3K/Akt pathway, pentose phosphate pathway, abnormal epigenetic modifications et al. (Giacomini et al., 2020; Navaei et al., 2022; Zhang et al., 2014). The other mechanisms by which β‐elemene sensitizes NSCLC cells to chemotherapeutics are far from being fully clarified.…”

Transcriptome analysis reveals PRKCA as a potential therapeutic target for overcoming cisplatin resistance in lung cancer through ferroptosis

“…1 C). which are involved in the regulation of cisplatin resistance in various tumors [ [24] , [25] , [26] ]. Subsequently, GSEA was performed to evaluate the enriched gene signatures related to canonical signaling pathways in cancer cells.…”

Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway

“…The development of cisplatin resistance results from the interaction of multiple complex factors involving the regulation of several cellular signaling pathways. In recent years, increasing evidence [19][20][21] has shown that the PI3K/AKT/MAPK3 pathway plays a crucial role in cisplatin resistance and that its aberrant activation is closely related to the resistance phenomenon. The PI3K/AKT/ MAPK signaling pathway is an important cell signaling pathway involved in the regulation of life activities such as cell survival, proliferation, differentiation, and apoptosis [22][23][24][25].…”

“…The AKT signaling pathway plays a key role in cell survival, proliferation, and drug resistance. The high expression of KIF2C may lead to the overactivation of the PI3K/ AKT pathway, enhance cell survival signaling, and reduce cell apoptosis in response to cisplatin-induced apoptosis [20]. In addition, KIF2C overexpression may promote the activation of the MAPK3 signaling pathway by interacting with MAPK3, which is involved in cell proliferation, differentiation, and survival and is closely related to tumorigenesis and drug resistance.…”