Aim
The aim of the present study was to establish a patient-derived xenograft (PDX) mouse model of non-small cell lung cancer (NSCLC) and investigate the anti-tumor efficacy of silencing of TUG1 and LCAL6 long non-coding RNA in the PDX model. Materials and
Conclusion
PDX NSCLC models were established with a high degree of similarity with the original tumor with regard to histological, immunohistochemical features and RNA expression of TUG1 and LCAL6. Silencing of TUG1 inhibited both tumor growth and expression of the proliferation marker Ki67 and HOX-gene family HOXB7 in the PDX model of NSCLC.
Methods
PDXs were established by subcutaneously implanting NSCLC surgical tumor fragments into immunodeficient mice. PDX characterization was performed by histopathological, immunohistochemical and real-time polymerase chain reaction (RT-PCR) analyses for NSCLC subtype-specific markers and expression of LCAL6 and TUG1. Anti-tumor efficacy of siRNA silencing of TUG1 and LCAL6 was also investigated in the PDX model. The effect of TUG1 and LCAL6 silencing on protein expression of proliferation marker Ki67 and HOX-gene family HOXB7 in the tumors was assessed by immunohistochemical staining and Western blotting.
Results
Establishment of NSCLC PDX models resulted in 9 of 26 cases (34.6%). Lung squamous cell carcinomas (SCC) had a higher engraftment rate (58.3%) than lung adenocarcinomas (ADC) (18.2%) (p<0.05). Comparative analysis indicated these established PDX models of NSCLC closely resembled the original tumors with regard to NSCLC subtype-specific markers TTF-1, napsin A, p63 and expression of LCAL6 and TUG1. The tumor volume and weight were significantly reduced in the TUG1-silenced group as compared to the control group (p<0.05). However, no significant tumor growth inhibition was found in the LCAL6-silenced group (p>0.05). Expression of both TUG1and LCAL6 was reduced by siRNA treatment. Expression of Ki67 and HOXB7 was significantly suppressed in both the TUG1- and LCAL6-silenced groups compared to the control group (p<0.01). The TUG1-silenced group showed more reduced Ki67 expression than the LCAL6-silenced group (p<0.05).