Insulin Receptor Substrate 1 Is Involved in the Phycocyanin-Mediated Antineoplastic Function of Non-Small Cell Lung Cancer Cells.

Shuai Hao,Qi Yang,Jing Wang,Qiancheng Li,Chengtao Wang,Fannian Li,Yuanpu Liu

doi:10.3390/molecules26164711

Abstract

Phycocyanin, derived from marine algae, is known to have noteworthy antineoplastic properties. However, the underlying mechanism involved in phycocyanin-mediated anti-growth function on non-small cell lung cancer (NSCLC) cells is still ambiguous. Here, we investigated the mechanism of action of phycocyanin on H1299, A549, and LTEP-a2 cells. According to the results obtained, insulin receptor substrate 1 (IRS-1) expression was reduced by phycocyanin. Cell phenotype tests showed that siRNA knockdown of IRS-1 expression significantly inhibited the growth, migration, colony formation, but promoted the apoptosis of NSCLC cells. Meanwhile, phycocyanin and IRS-1 siRNA treatment both reduced the PI3K-AKT activities in NSCLC cells. Moreover, overexpression of IRS-1 accelerated the proliferation, colony formation, and migration rate of H1299, A549, and LTEP-a2 cells, which was contradicting to the knockdown results. Overall, this study uncovered a regulatory mechanism by which phycocyanin inhibited the growth of NSCLC cells via IRS-1/AKT pathway, laying the foundation for the potential target treatment of NSCLC.

Highlights

The incidence and mortality rate of lung cancer is increasing at an alarming rate worldwide [1]
We have demonstrated that phycocyanin (4.8 μM) exerted significantly antineoplastic function on multiple Non-small cell lung cancer (NSCLC) cell lines including A549 (Figure S1), H1299, and LTEP-a2 cells [31]
To verify whether phycocyanin could reduce the expression of insulin receptor substrate 1 (IRS-1) in NSCLC cells, we performed Quantitative Real-Time PCR (qRT-PCR) and Western blot assay

Summary

Introduction

The incidence and mortality rate of lung cancer is increasing at an alarming rate worldwide [1]. An estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths occurred in 2020 [2]. Lung cancer is the leading cause of cancer death (18%). Similar to most malignant tumors, lung cancer is composed of cell subpopulations with different molecular characteristics, leading to heterogeneity within the tumor [5]. Non-small cell lung cancer (NSCLC), one of the subtypes of lung cancer, takes up approximately 85% of lung cancer cases [6], with characteristics of such as metastasis, low cure rate, and high mortality [7]. Substantial progresses have been made in the emergence of various targeted therapies and the effective application of immunotherapy on NSCLC [8]. Continuous drug development provides increasing patients with the hope of prolonging survival

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Results

Conclusion