Abstract
Aim: Liver cancer is one of the most common malignancies and has a high recurrence rate. However, current treatment strategies do not achieve satisfactory outcomes in the clinic. To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer, we investigated whether dichloroacetate (DCA) could enhance the sensitivity of liver cancer cells to pirarubicin (THP).Methods: Liver cancer cells were treated with DCA alone, THP alone, or DCA and THP combined. Cell viability was determined by the CCK-8 assay. Cell apoptosis was analyzed by flow cytometer. Reactive oxygen species (ROS) were detected using a CM-H2DCFDA fluorescence probe. Protein levels were identified by immunoblotting.Results: The results revealed that DCA significantly enhanced the antitumor effect of THP in liver cancer cells. Changes in morphology and adherence ability were observed, as well as decreased cell viability. The results of flow cytometry showed that the combination of THP and DCA significantly increased apoptosis of liver cancer cells. Moreover, compared with THP alone, combination treatment with DCA significantly increased THP-triggered ROS generation in liver cancer cells. The antioxidant N-acetyl-L-cysteine reversed the synergistic effect of DCA and THP on ROS generation, cell viability and apoptosis. Furthermore, phosphorylation of c-Jun N-terminal kinase (JNK) was significantly increased in the DCA and THP combination group. The effects of DCA and THP on cell viability and apoptosis were inhibited by the JNK inhibitor SP600125.Conclusion: The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the ROS-JNK signaling pathway.
Highlights
Liver cancer is the third leading cause of cancer mortality worldwide[1]
The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the Reactive oxygen species (ROS)-JNK signaling pathway
The present study investigated the effect of THP and DCA on the viability of liver cancer cells using the Cell Counting Kit-8 (CCK-8) assay
Summary
Liver cancer is the third leading cause of cancer mortality worldwide[1]. Thermal ablation and liver transplantation are current treatments for early-stage liver cancer[2]. Liver cancer is often diagnosed at an advanced stage and is associated with poor prognosis. Pirarubicin hydrochloride (THP), a novel anthracycline anticancer drug, has been widely used in transcatheter arterial chemoembolization (TACE) for the treatment of primary liver cancer[3,4]. THP exhibits a wide antineoplastic spectrum, strong antitumor activity and minimal toxicity[5]. 50% patients with liver cancer do not respond to initial TACE, due to tumor response and chemotherapeutic resistance[6,7]. The identification of novel drug combinations may overcome chemoresistance and improve patient outcomes
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
