RT Journal Article
SR Electronic
T1 An unconventional cancer-promoting function of methamphetamine in hepatocellular carcinoma
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201660
DO 10.26508/lsa.202201660
VO 6
IS 3
A1 Si, Zizhen
A1 Yang, GuanJun
A1 Wang, Xidi
A1 Yu, Zhaoying
A1 Pang, Qian
A1 Zhang, Shuangshuang
A1 Qian, Liyin
A1 Ruan, Yuer
A1 Huang, Jing
A1 Yu, Liu
YR 2023
UL http://www.life-science-alliance.org/content/6/3/e202201660.abstract
AB For the past decade, the prevalence and mortality of methamphetamine (METH) use have doubled, suggesting that METH use could be the next substance use crisis worldwide. Ingested METH is transformed into other products in the liver, a major metabolic organ. Studies have revealed that METH causes deleterious inflammatory response, oxidative stress, and extensive DNA damage. These pathological damages are driving factors of hepatocellular carcinoma (HCC). Nonetheless, the potential role of METH in HCC and the underlying mechanisms remain unknown. Herein, we found a higher HCC incidence in METH abusers. METH promoted cellular proliferation, migration, and invasion in two human-derived HCC cells. Consistently, METH uptake promoted HCC progression in a xenograft mouse model. Mechanistically, METH exposure induced ROS production, which activated the Ras/MEK/ERK signaling pathway. Clearance of ROS by NAC suppressed METH-induced activation of Ras/ERK1/2 pathways, leading to arrest of HCC xenograft formation in nude mice. To the best of our knowledge, this is the first study to substantiate that METH promotes HCC progression and inhibition of ROS may reverse this process.