The Research On Phenomenon And Mechanism Of Drug Resistance Of Hepatocellular Carcinoma Associated With Sox9by Regulating The Expression Of ABCG2

Hepatocellular carcinoma (HCC) is the fifth most common cancer in theworld and the third leading cause of cancer-related death. Hepatitis B virus(HBV) infection is a major risk factor for HCC. Surgical resection is acurative therapy for patients with resectabletumors and preserved liverfunction. However, a significant proportion of patients develop tumorrecurrence, whichtogether with concomitant hepaticdecompensation, is themain cause of death on long-term follow-up.However, according tothe widely accepted Barcelona Clinic LiverCancer (BCLC) staging system, those curative methods are generallylimitedto early-stage HCC patients, whereas more patients arefound withintermediate or advanced stage tumors whendiagnosed, thus are not eligiblefor curative treatment. The effectiveness of noncurative therapies includingtranscatheterarterial chemoembolization (TACE) and Sorafenibareunsatisfactory, which can only improve overall survivalby several months.Thedilemma of HCC treatmentis largely contributed by the highly malignantbehavior ofHCC, including early intrahepatic/systemic metastasisandmultidrug resistance. Drug resistance of tumor cells towardschemotherapeutic drug is the main reason for failure ofchemotherapy.Sex-determining Region Y (SRY) box9(SOX9) is a member ofa highly conserved family of transcriptionfactors defined by their similarity to the highmobility group DNA-binding domain of SRY. SOX9is also expressedand implicatedin the growth of cancers derived from several different celltypes. These diverse effects of SOX9arise from rolescontrolling thepericellular environment, cell differentiationand proliferation. Here, wereview these roles of SOX9in developmental and disease settings and discussthe potential for SOX9and its modulation as a strategy for diagnosing,predicting and treating disease. In our study, immunohistochemical analysisrevealed that SOX9staining was mainly localized in the nucleus of HCCcells.We found some HCC tissues with high SOX9expression and some HCCtissues with low SOX9expression, while some adjacent nonneoplastic livertissues with high SOX9expression and some adjacent nonneoplastic livertissues with low SOX9expression. Elevated SOX9expression has beenassociated with lower postoperative survival rates. The expression levels ofSOX9protein and mRNA in HCC tissues with high stage (III-IV) were bothsignificantly stronger than those with low stage. Silencing of Sox9expressioninhibited the proliferation and drug resistance potential of HCC cells.Compared with blank control and the scrambled negative control siRNA, theproliferation was significantly inhibited by siRNA-mediated Sox9knockdown.As an important multidrug resistance transporter, ABCG2has the capabilityof efflux various chemotherapy drugs and may contribute to drug resistance of cancer cells. We found the expression of Sox9was associated with theexpression of ABCG2. The mechanism of drug resistance of hepatocellularcarcinoma may be associated with Sox9by regulating the expression ofABCG2. The specific mechanism need further study.