Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration-dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time-dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia.

Pancreatic cancer significantly affects the quality of life due to the severe abdominal pain. However, the underlying mechanism is not clear. This study aimed to determine the relationship between substance P (SP) and pancreatic cancer perineural invasion (PNI) as well as mechanism of SP mediating pancreatic cancer PNI which cause pain in patients with pancreatic cancer. Human pancreatic cancer cells MIA PaCa-2, BxPC-3 and newborn dorsal root ganglions (DRGs) were used to determine the expression of SP or NK-1R in pancreatic cancer cells and DRGs cells by QT-PCR and Western blotting. The effects of SP on pancreatic cancer cell proliferation and invasion were analyzed using MTT assay and Transwell matrigel invasion assay, respectively. Alterations in the neurotropism of pancreatic cancer cells were assessed by co-culture system which mimics the interaction of tumor/neuron in vivo. SP is not only widely distributed in the neurite outgrowth from newborn DRGs but also expressed in MIA PaCa-2 and BxPC-3 cells. NK-1R is found to be overexpressed in the pancreatic cancer cell lines MIA PaCa-2 and BxPC-3. SP induces cancer cell proliferation and invasion and the expression of MMP-2 in pancreatic cancer cells; and NK-1R antagonists inhibit these effects. Furthermore, SP is also able to promote neurite outgrowth and the migration of pancreatic cancer cell cluster to the DRGs, which is blocked by NK-1R antagonists in the co-culture model. Our results suggest that SP plays an important role in the development of pancreatic cancer metastasis and PNI, and blocking the SP/NK-1R signaling system is a novel strategy for the treatment of pancreatic cancer.

The vital roles of long noncoding RNAs (lncRNAs) in the nonsmall cell lung cancer (NSCLC) tumorigenesis are increasingly important. This work aims to investigate the role of lncRNA LINC00460 in the gefitinib resistance of NSCLC cells and discover its relevant mechanism. Our finding reveals that the expression of lncRNA LINC00460 is upregulated in the gefitinib-resistant NSCLC tissue and cells, and closely correlated with advanced tumor stage and clinical poor prognosis outcome. Gain and loss functional assays are performed in gefitinib-resistant NSCLC cells (A549/GR), stating that LINC00460 facilitates the 50% inhibitive concentration of gefitinib for NSCLC cells, multidrug-resistant-related proteins (P-gp, MRP1, and BCRP), as well as the invasion. In vivo, LINC00460 silencing represses the tumor growth. Bioinformatics prediction tools and luciferase analysis confirm that the upregulated LINC00460 sponged miR-769-5p in NSCLC cells; moreover, epidermal growth factor receptor (EGFR) is identified as a direct target gene of miR-769-5p. Verification experiments confirm that the restoration of EGFR could weaken the sensibility of NSCLC cells toward the gefitinib. In conclusion, our result demonstrates that LINC00460 plays a pivotal role in gefitinib resistance of NSCLC cells by targeting EGFR through sponging miR-769-5p. This finding might serve as a therapeutic target for NSCLC.

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