Panoply™ Human PARP1 Knockdown Stable Cell Line

Lymph node metastasis and distant metastasis are significant limiting factors in the treatment of unresectable locally advanced (stage IIIB) and oligometastatic (stage IVa) lung cancer. Here, researchers found that 3-hydroxybutyrate dehydrogenase 1 (BDH1) is associated with lung cancer proliferation and metastasis. BDH1 expression in both tissue and serum samples was correlated with lung cancer metastasis. Mechanistic studies revealed that the PARP1-mediated AMPK-mTOR signaling pathway plays a crucial role in BDH1-induced autophagy. Activation of the mTOR pathway significantly enhanced the effects of BDH1 on cell proliferation and metastasis. These results were validated by knocking down PARP1 expression. Furthermore, in an H460 xenograft mouse model, in vivo administration of BDH1 effectively promoted tumor growth. These findings not only suggest that BDH1 may serve as a novel biomarker and therapeutic target for lung cancer metastasis but also indicate that the PARP1-mediated AMPK-mTOR signaling pathway may play a key role in BDH1-induced autophagy and lung cancer proliferation and metastasis.

To investigate the role of the PARP1/AMPK/mTOR pathway in lung cancer cell proliferation and metastasis, researchers treated PC-9 cells with rapamycin and performed lentiviral transfection. The results showed that the growth, migration, and invasion abilities of PARP1-knockdown cells were significantly reduced (Figure 1A-C). Conversely, rapamycin reversed the effects caused by PARP1 gene knockdown. Rapamycin significantly enhanced the growth, migration, and invasion abilities of PARP1-knockdown cells. These results indicate that rapamycin treatment reversed the proliferation and migration inhibition caused by PARP1 downregulation. As shown in Figure 1D, after starving PARP1-knockdown cells with Hank's buffer for 4 hours, the expression level of LC3-II in PC-9 cells was significantly decreased, while the expression level of P62 was significantly increased. However, rapamycin treatment reversed the effects of PARP1 gene knockdown. Immunofluorescence and electron microscopy further verified the role of PARP1 in autophagy (Figure 1E). Rapamycin treatment enhanced PARP1-induced autophagy. Therefore, the PARP1/AMPK/mTOR pathway may play an important role in lung cancer cell autophagy.

Figure 1. Effects of PARP1/mTOR/autophagy signalling pathway on lung cancer cell growth, migration and invasion. (Zhang Z, et al., 2023)