Objective To preliminarily investigate the relationship of Peg10 with focal adhesion kinase( FAK)- mediated cell adhesion-mediated drug resistance( CAM- DR) in hepatocellular carcinoma( HCC),and to explore the underlying molecular mechanism. Methods The effects of 5- fluorouracil( 5- Fu) and adriamycin( ADR) on the proliferation of LO2 cells,ADR- resistant human HCC cells BEL- 7404 / ADR( 7404 / ADR),and Peg10- silenced cells siRNA- BEL- 7404 / ADR( siRNA- 7404 / ADR) were examined by MTT assay.To build a tumor- bearing nude mouse model,48 rats were randomly divided into six groups( n = 8 each) : groups A,C,and D were injected with 7404 / ADR cells; groups B,E,and F were injected with siRNA- 7404 / ADR cells. For experimental treatments,groups A and B revived saline by intravenous injection through the tail vein; groups C and E were given 5- Fu; groups D and F received ADR by intravenous injection through the tail vein; tumor mass volume was measured after injection. Peg10 mRNA expression was assayed by RT- PCR,and PEG10,p- FAK,p- JNK,p- ERK,and p- P38 protein expression was assayed by Western blotting. Results The 24- h IC50 values of ADR and 5- Fu on SiRNA- 7404 / ADR were both significantly reduced compared with those on 7404 / ADR( t = 7. 641 and 7. 560,respectively; both P < 0. 01). Significantly smaller tumor mass volume was observed in groups B,C,and D than in group A( P < 0. 05),and in groups E and F than in group B( P < 0. 01). Additionally,tumor mass volume was significantly different between groups E and C as well as between groups F and D( P < 0. 05). PEG10 mRNA was rarely expressed in groups B,E,and F. Compared with that in group A,PEG10 mRNA expression in groups C and D was relatively reduced. PEG10 protein was rarely expressed in group B and its expression level significantly differed from that in group A( P < 0. 01). Additionally,there were statistically significant differences in p- FAK,p- JNK,p-ERK,and p38 MAPK protein expression between groups B and A( P < 0. 05). In groups C and D,PEG10,p- FAK,p- JNK,p- ERK,and p38 MAPK protein expression was significantly reduced compared with that in group A( P < 0. 05). Significant differences in p- FAK,p- JNK,p- ERK,and p38 MAPK protein expression also occurred in groups E and F compared with group B( P < 0. 01). Moreover,there were significant differences in PEG10,p- FAK p- JNK,p- ERK,and p38 MAPK protein expression between groups C and E as well as between groups D and F( P < 0. 01). Conclusion The inactivation of PEG10 can increase the sensitivity of ARD- resistant cell line BEL- 7404 to 5- Fu and ARD. The underlying mechanism is possibly related to down- regulation of p- FAK,p- JNK,p- ERK,and p38 MAPK expression.