Abstract
Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.
Highlights
Human hepatocellular carcinoma (HCC) is one of the most common malignancies all around the world, especially in Asia (Norsa’adah et al, 2013; Wiangnon et al, 2012)
Epirubicin (EPI), an anthracycline antitumour antibiotic which is structurally related to doxorubicin, is among the most active single agents used in the management of patients with breast cancer and other human tumour cells
The lysates were boiled for 5 min, separated by 15% SDS-PAGE, and transferred to polyvinylidene difluoride (PVDF) membranes (Pall Corporation) in transblotting buffer (25 mM Tris, 192 mM glycine, 20% v/v methanol, pH 8.3)
Summary
Human hepatocellular carcinoma (HCC) is one of the most common malignancies all around the world, especially in Asia (Norsa’adah et al, 2013; Wiangnon et al, 2012). The high incidence of tumor recurrences, possibly from micrometastasis of tumor cells prior to curative surgery, further reduces patients’ 5-year survival (Li et al, 2013; Zhu et al, 2013). This cancer seems to be stubborn as it is resistant to any chemical agents developed until now and chemical therapies used to treat cancer are highly toxic and often nonspecific (Kong et al, 2013). Comparative and noncomparative clinical trials have demonstrated that regimens containing conventional
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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
