Abstract
Low temperature plasma (LTP) has emerged as a new research hotspot of promising therapy to fight against cancer. Autophagy is a multifunctional process that digests and recycles cellular contents within lysosomes to maintain homeostasis, which is the underlying mechanism of cancer cell death and anti-cancer treatment. This study aimed at investigating whether autophagy of HepG2 cells could be induced by LTP and revealing the related molecular mechanism. For this purpose, the atmospheric pressure plasma jet (APPJ) in helium was utilized to generate plasma-actived medium (PAM) to treat HepG2 cells in vitro. Catalase (CAT), superoxide dismutase (SOD) and 3-methyladenine (3-MA) were respectively added into the PAM as the intervention group. The cell viability, formation of autophagosomes, intracellular reactive oxygen species (ROS) level, expression levels of autophagy-associated proteins and key proteins involved in PI3K/AKT/mTOR pathways were detected. The results showed that LTP inhibited cell viability in a dose- and time-dependent manner. Autophagy was induced through the formation of autophagosomes, conversion of LC3-II/LC3-I, increased expression of beclin 1 and degradation of p62. The mechanism was deduced that LTP enhanced the intracellular ROS level and decreased the phosphorylation level of key proteins in PI3K/AKT/mTOR/p70S6K pathway. However, these effects were blocked by the autophagy inhibitor 3-MA and ROS scavengers (CAT and SOD). The therapeutic efficacy of LTP against HepG2 cells may involve autophagy via suppressing PI3K/AKT/mTOR signaling pathway by LTP-mediated ROS.
Highlights
IntroductionHepatocellular carcinoma (HCC), an extraordinarily heterogeneous malignancy, is the second leading cause of cancer deaths worldwide. Over the past few years, early diagnoses and treatments of HCC have achieved continual amelioration and refinement, but the therapies for most advanced patients are still considered as insufficient and ineffective. Surgical resection has been deemed as the optimal therapy, but only a small proportion of patients qualify for surgery and the metastatic diseases continually develop even after potentially curative surgery. Patients with HCC are proverbially resistant to systemic chemotherapy, and sorafenib as the prescriptive first-line targeted systemic drug for advancedHCC has been demonstrated limited survival benefits with very low response rates. it is critical to develop novel and effective treatments for this devastating disease.Autophagy is an adaptive catabolic and multifunctional process that digests and recycles cellular contents within lysosomes and presents a considerable aspect in cellular homeostasis
The anti-cancer capacity of Low temperature plasma (LTP) treatment could be regulated by controlling the treatment time, which was demonstrated in treatment of several types of tumor cells
LTP increased the formation of autophagosomes, as well as conversion of light chain 3 (LC3)-II/LC3-I, expression of beclin 1, degradation of p62 and inhibited the PI3K/AKT/mTOR pathways as the treatment time prolonged
Summary
Hepatocellular carcinoma (HCC), an extraordinarily heterogeneous malignancy, is the second leading cause of cancer deaths worldwide. Over the past few years, early diagnoses and treatments of HCC have achieved continual amelioration and refinement, but the therapies for most advanced patients are still considered as insufficient and ineffective. Surgical resection has been deemed as the optimal therapy, but only a small proportion of patients qualify for surgery and the metastatic diseases continually develop even after potentially curative surgery. Patients with HCC are proverbially resistant to systemic chemotherapy, and sorafenib as the prescriptive first-line targeted systemic drug for advancedHCC has been demonstrated limited survival benefits with very low response rates. it is critical to develop novel and effective treatments for this devastating disease.Autophagy is an adaptive catabolic and multifunctional process that digests and recycles cellular contents within lysosomes and presents a considerable aspect in cellular homeostasis.. Hepatocellular carcinoma (HCC), an extraordinarily heterogeneous malignancy, is the second leading cause of cancer deaths worldwide.. Over the past few years, early diagnoses and treatments of HCC have achieved continual amelioration and refinement, but the therapies for most advanced patients are still considered as insufficient and ineffective.. Surgical resection has been deemed as the optimal therapy, but only a small proportion of patients qualify for surgery and the metastatic diseases continually develop even after potentially curative surgery.. Patients with HCC are proverbially resistant to systemic chemotherapy, and sorafenib as the prescriptive first-line targeted systemic drug for advanced. HCC has been demonstrated limited survival benefits with very low response rates.. It is critical to develop novel and effective treatments for this devastating disease.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
