Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.

Tse-Hung Huang,Chien-Yin Liu,Chang-Jer Wu,Yi-Han Chiu,Cheng-Ta Yang,Yi-Lin Chan,Jyh-Sheng You,Hang Wang,Tzung-Yan Lee,Kuang-Hung Hsu,Tsung-Lin Li

doi:10.18632/oncotarget.4348

Abstract

Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death.

Highlights

Lung cancer known for its high relapse and low cure rate is the leading cancer, accounting for 19.5% of all cancer death [1], wherein the non-small-cell lung cancer (NSCLC) takes up 75–80% with a five-year survival rate of 10–15%
To make sure whether Antrodia cinnamomea (AC) differentially protects hepatic cells but inhibits lung carcinoma cells, we examined cell viability and survival rate in the presence of AC by MTS assay
In terms of cell viability and proliferation, HepG2 cells treated with cisplatin or/and AC resulted in quite distinct results as shown in Figure 1: AC does not inhibit the viability of HepG2 cells, while cisplatin has strong cytotoxicity to HepG2 cells in a dose-dependent manner

Summary

Introduction

Lung cancer known for its high relapse and low cure rate is the leading cancer, accounting for 19.5% of all cancer death [1], wherein the non-small-cell lung cancer (NSCLC) takes up 75–80% with a five-year survival rate of 10–15%. The fact is that cisplatin-based adjuvant chemotherapy has been estimated with high overall survival and/or disease-free survival rate in five large-scale clinical trials over 4584 fully NSCLC resected patients [9]. Both disease-free and overall survival rates of the NSCLC resected patients were increased by coadministration of cisplatin and vinorelbine [10]. Hepatotoxicity is very common in patients under high-dose cisplatin treatment [15] Poor outcomes such as low survival rate, bad tumor responses, deteriorated life quality, and ill toxicity in advanced NSCLC patients underline urgent needs for better treatments [17]

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