Effect of danusertib on cell cycle, apoptosis and autophagy of hepatocellular carcinoma HepG2 cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of danusertib (Danu), an inhibitor of Aurora kinase, on the proliferation, cell cycle, apoptosis, and autophagy of hepatocellular carcinoma HepG2 cells and explore the underlying mechanisms.@*METHODS@#MTT assay was used to examine the effect of Danu on the viability of HepG2 cells to determine the IC50 of Danu. The effect of Danu on cell cycle distribution, apoptosis and autophagy were determined using flow cytometry. Western blotting was used to detect the expressions of the proteins related to cell cycle, apoptosis and autophagy. Chloroquine was used to suppress Danuinduced autophagy to test the apoptosis-inducing effect of Danu.@*RESULTS@#Danu significantly inhibited the proliferation of HepG2 cells with IC of 39.4 μmol and 14.4 μmol at 24 h and 48 h, respectively. Danu caused cell cycle arrest in G/M phase in HepG2 cells and led to polyploidy accumulation via up-regulating the expressions of p53 and p21 and down-regulating the expressions of cyclin B1 and DC2. Danu also caused apoptosis of HepG2 cells through up-regulating the expressions of Bax, Puma, cleaved caspase-3, cleaved caspase-9, cleaved PARP and cytochrome C and down-regulating the expressions of Bcl-xl and Bcl-2. Danu induced autophagy via activating AMPK signaling and inhibiting PI3K/PTEN/AKT/mTOR axis, and inhibition of Danu-induced autophagy with chloroquine enhanced the pro-apoptotic effect of Danu.@*CONCLUSIONS@#Danu inhibits cell proliferation and induces cell cycle arrest in G/M phase, apoptosis and cytoprotective autophagy in HepG2 cells.

Percutaneous intratumoral injection of lipiodol and chemotherapeutic agents emulsion for primary liver cancer / 中华普通外科杂志

Objective To evaluate percutaneous intratumoral injection of chemotherapeutic agents lipiodol emulsion (CALE) for the treatment of primary liver cancer. Methods This study included 57 patients of hepatocellular carcinoma (n=49) and intrahepatic cholangiocarcinoma (n=8).53 were male and 4 were female,with a mean age of 48.02 years(range,19～70 years).In all,ninety CALE injections were assigned to 90 target areas within the lesions.Before the procedures,transcathetcr arterial chemoembolization (n=55) or infusion (n=2) was carried out in these patients.By arteriography,low blood supply of target areas was showed or it was concluded that superselective catheterization of supply arteries of lesions could not accomplished.Percutaneous intratumoral CALE injection was carried out under fluoroscopy or CT guidance.Therapeutic effect,side effect and complications were assessed based on clinical manifestation,laboratory examination and fluoroscopy or CT one week after procedure.Follow-up was carried out after 1,3,6 months and 1 year,and once every six months thereafter.Local recurrences were treated according to patients'will.Results 90 sessions of percutaneous injection were successfully performed on 57 patients,with 100% technique success rate.The volume of CALE iniected per session ranged 3.0-7.0 ml(mean,6.0 ml) in target size less than 3 cm,12.0-20 ml(mean,15 ml)in target size of 3-5 cm and 24-40 ml in target larger than 5 cm.Serum AFP was positive in 43 patients and decreased to normal in 14 patients(28%).54 lesions(60%)were with well distribution of the lipiodol-chemotherapy mixture on CT 1 month after procedure.Follow-up ranged from 2 months to six years(mean,16 months).The median survival time was 400 d.The cumulative survival rates at 200 d,600d was 85%and 30%,respectively.Complications included fever (n=22,24.4%),nausea and vomit(n=11,12.2%),and pain at the puncture site (n=17,18.9%).Conclusions Percutaneous intratumor CALE injection is safe and effective for the treatment of primary liver cancer.