Programmed cell death factor 4 enhances the chemosensitivity of colorectal cancer cells to Taxol

Abstract

Drug resistance and disease relapse are still challenging problems in the chemotherapy of colorectal cancer (CRC). Programmed cell death factor 4 (PDCD4) has previously been reported to act as a tumor suppressor and was implicated in the chemosensitivity of numerous types of human malignancy. In this study, the effect of PDCD4 in the sensitivity of CRC to the chemotherapy drug Taxol was investigated. The results confirmed that lower PDCD4 expression was present in CRC tumor tissues, when compared with in normal adjacent tissues (p) and closely associated with the prognosis of patients with CRC. Upregulation of PDCD4 significantly enhanced the sensitivity of CRC cells to Taxol, by partially contributing to pro-apoptosis and anti-invasion pathways, both through upregulation of the apoptosis-associated protein Bax, and downregulation of the anti-apoptosis protein Bcl-2 and invasion-associated proteins MMP-9. These findings might present a novel strategy for sensitizing tumor cells to apoptosis and, thus, overcoming chemotherapy resistance in CRC.

Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells

“…Further studies on the use of PDCD4 as a prognostic biomarker are warranted. There may also be a role for PDCD4 as a predictive biomarker given its potential impact on sensitizing tumors to anti-neoplastic agents and radiation [ 24 , 31 , 32 , 33 , 34 , 58 ].…”

“…PDCD4 can inhibit neoplastic transformation, tumor angiogenesis and invasion, and/or induce apoptosis [ 23 , 29 ]. Furthermore, PDCD4 downregulation in tumor cells is associated with drug resistance, whereas its expression enhances sensitivity to chemo- and radio-therapy [ 24 , 31 , 32 , 33 , 34 ]. Besides its primary function in carcinogenesis, a new role for PDCD4, as a regulator of the inflammatory process has recently emerged [ 29 , 35 ].…”

Low GAS5 expression may predict poor survival and cisplatin resistance in cervical cancer

“…PDCD4, which is originally found to participate in apoptosis, can selectively enhance chemosensitivity to platinum compounds mainly through the death receptormediated pathway 54 . Usually downregulated in tumours [55][56][57] , PDCD4 can inhibit neoplastic transformation, control translation and induce apoptosis 58 . PDCD4 overexpression activated caspases 8, 9, 3, lead to the apoptosis of liver cancer cells 59 .…”

In silico ADME and molecular simulation studies of pharmacological activities of phytoconstituents of Annona muricata (L.) Fruit

“…PDCD4, an apoptosis-associated gene, is regulated by interleukins IL-2, IL-12, and IL-15, and functions as a tumor suppressor gene, playing essential roles in apoptosis, protein translation, signal transduction, and inflammation mediator stimu-lation (Zhang et al, 2014;Pin et al, 2020). Loss or downregulation of PDCD4 expression promotes tumor cell proliferation, invasion, and metastasis while reducing tumor cell apoptosis in various cancer types (Wang et al, 2019). PDCD4 downregulation is associated with chemoresistance, coinciding with a reduction in eukaryotic initiation factor-4A (eIF4A) interaction (González-Ortiz et al, 2022).…”

“…sion significantly enhances the chemosensitivity of various cancer cells, including acute myeloid leukemia, breast cancer, ovarian cancer, non-small cell lung cancer (NSCLC), rectal cancer, and pancreatic cancer, to chemotherapy drugs like dexamethasone and taxol (Shibahara et al, 1995;Wang et al, 2019). PDCD4 overexpression in lung tumor cells has been linked to the suppression of the transcriptional activation of Nrf2 through its negative regulator, Keap1 (Hwang et al, 2020).…”