The human absent in melanoma 2 (AIM2) is considered as a DNA recognizer. AIM2 has been described as a tumor suppressor gene in the early years. But recent studies suggested that it functions as an oncogene in several cancers. However, its roles in non-small-cell lung cancer (NSCLC) remain unclear. Here we reported that AIM2 highly expressed in NSCLC cells and exhibited a tumor-promoting property both in vitro and in vivo. Besides, AIM2 short hairpin RNA (shRNA)-mediated suppression of cell proliferation was triggered by the accumulation of cells at the G2/M phase.Knockdown of AIM2 reduced the inflammasome formation, while overexpression of AIM2 or stimulation by poly(dA:dT) induced the inflammasome formation. Interestingly, blockade of the inflammasome by caspase-1 inhibitor VX-765 or ASC small interfering RNA (siRNA) abolished the effects brought by AIM2 shRNA and AIM2 plasmid. In summary, our results revealed that AIM2 functioned as an oncogene in NSCLC in an inflammasome-dependent way.

Chemoresistance is a major therapeutic obstacle in the treatment of human pancreatic ductal adenocarcinoma (PDAC). As an oxidative stress responsive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of cytoprotective genes. Nrf2 not only plays a critical role in chemoprevention, but also contributes to chemoresistance. In this study, we found that digoxin markedly reversed drug resistance of gemcitabine by inhibiting Nrf2 signaling in SW1990/Gem and Panc-1/Gem cells. Further research revealed that digoxin regulated Nrf2 at transcriptional level. In in vivo study, we found that digoxin and gemcitabine in combination inhibited tumor growth more substantially when compared with gemcitabine treatment alone in SW1990/Gem-shControl cells-derived xenografts. In the meantime, SW1990/Gem-shNrf2 cells-derived xenografts responded to gemcitabine and combination treatment similarly, suggesting that digoxin sensitized gemcitabine-resistant human pancreatic cancer to gemcitabine, which was Nrf2 dependent. These results demonstrated that digoxin might be used as a promising adjuvant sensitizer to reverse chemoresistance of gemcitabine-resistant pancreatic cancer to gemcitabine via inhibiting Nrf2 signaling.

Our data strongly suggest that miR-205 plays an important role in endometrial cancer migration and invasion by targeting the AKT pathway. Our data highlight miR-205 as a potential molecular target for endometrial cancer treatment.

Better efficacy could be obtained by integrative medical therapy in treating PCT-MD.

Absent in melanoma 2 (AIM2) is a critical component in natural immunity system and is closely related to cancer initiation and development. It has been shown that AIM2 inhibited colorectal cancer (CRC) development and cell proliferation. It remains unresolved how AIM2 acts on CRC metastasis. In this study, we assessed migration, invasion ability, and epithelial‐mesenchymal transition (EMT) program upon AIM2 overexpression or knockdown in human CRC cells. Transwell assay demonstrated that upregulation of AIM2 reduced cell migration and invasion. Epithelial marker E‐cadherin was augmented and mesenchymal markers vimentin, as well as Snail, were examined decreased by Western blot, real‐time polymerase chain reaction, and immunofluorescence. Correspondingly, knockdown of AIM2 led to a reverse consequence. In addition, AIM2 regulated Akt phosphorylation and effects of AIM2 on cell invasion and EMT were recovered after administration of Akt inhibitor, suggesting that AIM2 suppressed EMT dependent on Akt pathway. In addition, caspase‐1 inhibitor exposure indicated that AIM2 abrogated EMT through the inflammasome pathway as well. In summary, AIM2 suppressed EMT via Akt and inflammasome pathways in human CRC cells.

Cisplatin based combination chemotherapy has become a conventional treatment for ovarian cancer. However, the appearance of drug resistance during the ovarian cancer treatment is one of the main obstacles for improving the therapeutic perspective of ovarian cancer. The aim of this study was to confirm the hypothesis that Hydroxysafflor yellow A (HYSA) can reverse chemotherapy resistance in ovarian cancer cells. In vitro study on A2780/DDP ovarian cell line was used to monitor cell proliferation by cytotoxicity assay and real time cellular analysis associated with flow cytometry that intend to determine if HSYA enhance cisplatin sensitivity through apoptosis. In vivo experiments on mice was used to identify the HYSA effects on cisplatin sensitivity. The in vitro studies showed that MAPK signal pathways were suppressed in cisplatin resistant ovarian cells A2780/DDP. Also, HSYA enhanced cisplatin sensitivity in cisplatin resistant organisms, in vivo. Mechanistically, HYSA increase P-JNK and P-38 levels, but has no effect on P-ERK, indicating that HYSA enhanced cisplatin sensitivity via JNK and P38 MAPK signalling pathways. RezumatChimioterapia bazată pe combinații cu cispaltin a devenit un tratament convențional pentru cancerul ovarian. Cu toate acestea, prevalența rezistenței medicamentoase în timpul tratamentului cancerului ovarian este unul dintre principalele obstacole în calea îmbunătățirii perspectivelor terapeutice. Scopul acestui studiu a fost confirmarea ipotezei că safflomin A (HYSA) poate inversa rezistența la chimioterapie în celulele cancerigene ovariene. Studiul in vitro asupra liniei celulare A2780/DDP a fost utilizat pentru a monitoriza proliferarea celulară prin analiza citotoxicității și analiza celulară în timp real asociată cu citometria în flux, pentru a determina dacă HYSA crește sensibilitatea la cisplatin. S-au realizat experimente in vivo, pe șoareci, pentru a identifica efectele HYSA asupra sensibilității la cisplatină. Studiile in vitro au arătat că semnalele celulare au fost suprimate în celulele ovariene A2780/DDP rezistente la cisplatină. De asemenea, HSYA a îmbunătățit in vivo sensibilitatea la cisplatină în organismele rezistente. HYSA a crescu nivelurile P-JNK și P-38, dar nu a avut niciun efect asupra P-ERK, indicând faptul că HYSA acționează prin intermediul căilor de semnalizare JNK și P38 MAPK.