Abstract
Recently, many researches have reported that antibiotic tigecycline has significant effect on cancer treatment. However, biomedical functions and molecular mechanisms of tigecycline in human pancreatic ductal adenocarcinoma (PDAC) remain unclear. In the current study, we tried to assess the effect of tigecycline in PDAC cells. AsPC‐1 and HPAC cells were treated with indicated concentrations of tigecycline for indicated time, and then, MTT, BrdU and soft agar assay were used to test cell proliferation. The effect of tigecycline on cell cycle and cellular apoptosis was tested by cytometry. Migration and invasion were detected by wound healing assay and transwell migration/invasion assay. Expressions of cell cycle‐related and migration/invasion‐related protein were determined by using Western blot. The results revealed that tigecycline observably suppressed cell proliferation by inducing cell cycle arrest at G0/G1 phase and blocked cell migration/invasion via holding back the epithelial‐mesenchymal transition (EMT) process in PDAC. In addition, tigecycline also remarkably blocked tumorigenecity in vivo. Furthermore, the effects of tigecycline alone or combined with gemcitabine in vitro or on PDAC xenografts were also performed. The results showed that tigecycline enhanced the chemosensitivity of PDAC cells to gemcitabine. Interestingly, we found CCNE2 expression was declined distinctly after tigecycline treatment. Then, CCNE2 was overexpressed to rescue tigecycline‐induced effect. The results showed that CCNE2 overexpression significantly rescued tigecycline‐inhibited cell proliferation and migration/invasion. Collectively, we showed that tigecycline inhibits cell proliferation, migration and invasion via down‐regulating CCNE2, and tigecycline might be used as a potential drug for PDAC treatment alone or combined with gemcitabine.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy in the digestive tract with a poor prognosis
We showed that antibiotic tigecycline blocks cell proliferation, migration and invasion via down-regulating Cyclin E2 (CCNE2) in PDAC cells
We demonstrated that tigecycline inhibits cell proliferation, migration and invasion and leads to cell cycle arrest in PDAC cells
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy in the digestive tract with a poor prognosis. C-Abl–specific tyrosine kinase inhibitors (TKIs) in combination with tigecycline were shown to be a promising strategy to treat patients with CML.[31] It has some side effects, such as hypofibrinogenemia,[32] mitochondrial dysfunction 33 and chronic otitis,[34] we cannot ignore its important potential promise in anti-cancer therapy. It seems that tigecycline has significance in inhibiting the cell viability of pancreatic cancer cell line MIA PaCa2 cells,[23] the exact effect and its model of action remain to be further explored. Tigecycline might be used as a promising new candidate anti-cancer agent for PDAC treatment alone or in combination
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