Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Zinc protoporphyrin IX improves the sensitivity of colorectal cancer cells to paclitaxel by inactivating AKT/mTOR pathway via HO-1

Quanfu Li¹, Tian Xia¹, Guowei Yang², Houlai Yang¹, Juan Zhang³

¹Department of General Surgery, Wuhan third Hospital (Tongren Hospital Affiliated with Wuhan University), Wuhan, Hubei 430000, China; ²Department of Traditional Chinese Medicine, The First Hospital Affiliated with Lanzhou University, China; ³Department of Proctology, The Hospital Affiliated with Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730000, China.

For correspondence:- Juan Zhang Email: zhangjuan_0531@163.com Tel:+8618709429225

Accepted: 13 December 2021 Published: 31 January 2022

Citation: Li Q, Xia T, Yang G, Yang H, Zhang J. Zinc protoporphyrin IX improves the sensitivity of colorectal cancer cells to paclitaxel by inactivating AKT/mTOR pathway via HO-1. Trop J Pharm Res 2022; 21(1):61-659 doi: 10.4314/tjpr.v21i1.10

© 2022 The authors.
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Abstract

Purpose: To examine the effect of zinc protoporphyrin IX (ZnPPIX) on the sensitivity of colorectal cancer (CRC) cells to paclitaxel.

Methods: Paclitaxel-resistant CRC cells were established by incubating CRC cells with increasing concentrations of paclitaxel. Colorectal cancer cells were incubated with ZnPPIX for 1 h before treatment with paclitaxel. Cell viability, proliferation, and apoptosis were determined by MTT, colony formation, and flow cytometry assays, respectively. The effect of ZnPPIX on DNA damage response in paclitaxel-resistant cells was assessed using western blot analysis of γH2AX, p-DNA-PK, and Rad51.

Results: Paclitaxel suppressed proliferation of SW480 cells at an IC₅₀ (half-maximal inhibitory concentration) of 0.23 μM, while that of proliferation of paclitaxel-resistant SW480 cells was also suppressed by paclitaxel at an IC₅₀ of 2.58 μM (p < 0.05). Incubation with ZnPPIX attenuated the paclitaxel-induced decrease in viability and proliferation of SW480 cells. Paclitaxel-induced apoptosis of SW480 cells was enhanced upon incubation with ZnPPIX (p < 0.05). Similarly, protein expression of γH2AX was enhanced while protein expressions of p-DNA-PK and Rad51 reduced in paclitaxel-induced SW480 cells. On incubation with ZnPPIX, protein expression of heme oxygenase-1 (HO-1) and AKT and mTOR phosphorylation decreased in SsW480 cells (p < 0.05).

Conclusion: ZnPPIX enhances paclitaxel-induced chemosensitivity of CRC by suppression of HO-1-mediated AKT/mTOR activation, and could potentially be used to facilitate the management of CRC.

Keywords: Zinc protoporphyrin IX, Paclitaxel, Chemosensitivity, Colorectal cancer, AKT/mTOR