Abstract
This study aimed to investigate the effects of BCRP expression on tumor recurrence, metastasis and treatment tolerability. A VX2 rabbit liver tumor model was established. Division was randomly into 4 groups: namely saline control group; A group, given hydration lipiodol; B group, Ad-p53; and C group, Ad-p53+hydration lipiodol. After the intervention, samples were collected to detect the BCRP, MMP-2, VEGF and PCNA. The expression of BCRP, MMP-2, PCNA and VEGF in tumors in Group A had no significant difference when compared with the control group, while in B and C group, the values were significantly lower (P < 0.05). BCRP positive expression in metastatic lesions significantly increased (P < 0.05), and was correlated with MMP-2 (X2=6.172, P = 0.0131). BCRP may play an important role in mediating liver cancer multidrug resistance to chemotherapy, and may be correlated with tumor recurrence and metastasis, which leads to weakened treatment effect. Ad-P53 can down-regulate the expression of related genes, playing a role in multidrug resistance reversal and increased sensitivity in liver cancer treatment.
Highlights
China is a highly-incident-liver-cancer country, with the number of new cases each year accounting for 55% of the whole world, and the incidence increases year by year. 80% clinical cases of liver cancer have lost the chances of operation before the treatment, though palliative care therapy via the hepatic artery chemoembolization intervention has achieved good short-term effects, and patients can survive with existence of tumor, the long-term outcome is not satisfactory (Song et al, 2012; Takayasu et al, 2012)
BCRP may play an important role in mediating liver cancer multidrug resistance to chemotherapy, and may be correlated with tumor recurrence and metastasis, which leads to weakened treatment effect
Studies have shown that tumor stem cells, contributing to the tumor recurrence and tolerance to the treatment, might be associated with high expression levels of ABC transporter proteins in stem cells (Bomken et al, 2010)
Summary
China is a highly-incident-liver-cancer country, with the number of new cases each year accounting for 55% of the whole world, and the incidence increases year by year. 80% clinical cases of liver cancer have lost the chances of operation before the treatment, though palliative care therapy via the hepatic artery chemoembolization intervention has achieved good short-term effects, and patients can survive with existence of tumor, the long-term outcome is not satisfactory (Song et al, 2012; Takayasu et al, 2012). Researches find that, multidrug resistance (MDR) is the most important cellular defense mechanism for malignant tumor to drug attack (Oh et al, 2010), and an important reason for treatment failure and tumor recurrence and metastasis, which is a problem urgent to be solved in clinic. Relevant basic and clinical researches on expression of MDR-associated factors have been reported (Robey et al, 2007; Abaan et al, 2009; Schwavedissen et al.,2010; Wittgen et al, 2011), while there is still no study about the impact of VX2-interventional treatment on MDR gene in rabbit liver cancer. The regulatory effect of Ad-P53 intervention on BCRP expression was observed, and the significance of gene therapy for MDR reversal and increase of tumor focus sensitivity to treatment were studied. The objective is to provide a basis for gene therapy and further improving the clinical therapeutic effect of MDR reversal agent, a new chemotherapy sensitizer
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