Zinc promotes prostate cancer cell chemosensitivity to paclitaxel by inhibiting epithelial‐mesenchymal transition and inducing apoptosis

Abstract

Background: Paclitaxel (PTX) is a first-line chemotherapeutic drug for the treatment of prostate cancer. However, most patients develop resistance and metastasis, and thus new therapeutic approaches are urgently required. Recent studies have identified widespread anti-tumor effects of zinc (Zn) in various tumor cell lines, especially prostate cancer cells. In this study, we examined the effects of Zn as an adjuvant to PTX in prostate cancer cells. Methods: PC3 and DU145 cells were treated with different concentrations of Zn and/ or PTX. MTT assay was used to detect cell viability. Real-time cell analysis (RTCA) and microscopy were used to observe morphological changes in cells. Western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. qPCR (reverse transcription-polymerase chain reaction) was used to examine changes in TWIST1 mRNA levels. Cell invasion and migration were detected by scratch and transwell assays. shRNA against TWIST1 was used to knockdown TWIST1. Colony formation assay was used to detect cell proliferation, while Annexin V and propidium iodide (PI) staining was used to detect cell apoptosis. Results: Zn and PTX increased proliferation inhibition in a dose-and time-dependent manner in prostate cancer cells, while Zn increased prostate cancer cell chemosensitivity to PTX. Combined Zn and PTX inhibited prostate cancer cell invasion and migration by downregulating the expression of TWIST1. Furthermore, knockdown of TWIST1 increased the sensitivity of prostate cancer cells to PTX. In addition, Zn and PTX reduced cell proliferation and induced apoptosis in prostate cancer cells.Conclusions: Our results demonstrated that Zn and PTX combined therapy inhibits EMT by reducing the expression of TWIST1, which reduces the invasion and migration of prostate cancer cells. SiTWIST1 increased the sensitivity of prostate cancer cells to PTX. In addition, with prolonged treatment, Zn and PTX inhibited proliferation and led to prostate cancer cell apoptosis. Therefore, Zn may be a potential adjuvant of PTX in treating prostate cancer and combined treatment may offer a promising therapeutic strategy for prostate cancer. K E Y W O R D S

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

“…Previous studies have also shown that the zinc level in hepatoma cells is significantly lower than that in normal liver cells, which is related to the carcinogenesis and progression of HCC [ 59 ]. Zinc released by ZIF-8 degradation may promote the sensitivity of cancer cells to chemotherapeutic drugs and inhibit the development of HCC [ 60 , 61 ]. These may partly explain why the As@ZIF-8 NPs group showed lower IC 50 values and less invasion and migration of residual cells than the ATO group.…”

Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

“…Moreover, quercetin was shown to suppress the EMT process, deactivating the PI3K/Akt signaling pathway and downregulating MALAT1, a long noncoding RNA [ 250 ]. Similarly, zinc’s synergistic effect to paclitaxel was demonstrated in PCa cell lines via EMT inhibition by downregulating the expression of TWIST1 [ 251 ].…”

Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression

“…Moreover, it causes G2/M arrest 10 . Some reports have indicated that PTX strongly induces cell apoptosis in multiple cancer cells, such as lung cancer cells, 11 breast cancer cells, 12 ovarian cancer cells 13 and PCa cell 14 . However, no report has shown the antitumor effect of NCTD combined with PTX in PCa cells.…”