Anlotinib Inhibits Cisplatin Resistance in Non-Small-Cell Lung Cancer Cells by Inhibiting MCL-1 Expression via MET/STAT3/Akt Pathway.

Background: Anlotinib is an effective targeted therapy for advanced non-small-cell lung cancer (NSCLC) and has been found to mediate chemoresistance in many cancers. However, the underlying molecular mechanism of anlotinib mediates cisplatin (DDP) resistance in NSCLC remains unclear. Methods: Cell viability was assessed by the cell counting kit 8 assay. Cell proliferation, migration, and invasion were determined using the colony formation assay and transwell assay. The mRNA expression levels of mesenchymal-epithelial transition factor (MET) and myeloid cell leukemia-1 (MCL-1) were measured by quantitative real-time PCR. Protein expression levels of MET, MCL-1, and STAT3/Akt pathway-related markers were examined using western blot analysis. Results: Our data showed that anlotinib inhibited the DDP resistance of NSCLC cells by regulating cell proliferation and metastasis. Moreover, MET and MCL-1 expression could be decreased by anlotinib treatment. Silencing of MET suppressed the activity of the STAT3/Akt pathway and MCL-1 expression. Furthermore, MET overexpression reversed the inhibitory effect of anlotinib on the DDP resistance of NSCLC cells, and this effect could be eliminated by MCL-1 knockdown or ACT001 (an inhibitor for STAT3/Akt pathway). Conclusion: Our results confirmed that anlotinib inhibited DDP resistance in NSCLC cells, which might decrease MCL-1 expression via mediating the MET/STAT3/Akt pathway.

Subarachnoid hemorrhage with Takotsubo syndrome as the prominent manifestation: A case and literature review.

Background: Takotsubo syndrome, which is often induced by physical or psychological stress, is typically a cardiac syndrome with transient left ventricular dysfunction in the absence of obstructive coronary artery disease. Subarachnoid hemorrhage with typical symptoms and signs is frequently reported, whereas the incidence of subarachnoid hemorrhage with Takotsubo syndrome as the prominent manifestation without a typical headache is rarely reported. Case description: We present a rare case of a 63-year-old male patient with cough and fever as the first manifestations, accompanied by mild dizziness, headache, and mental discomfort; however, the patient was eventually diagnosed with atypical subarachnoid hemorrhage with Takotsubo syndrome. The patient underwent general anesthesia downwards stent-assisted spring coil embolization and was discharged from the hospital after postoperative treatment consisting of anti-cerebrovascular spasm, anti-platelet aggregation, and cerebrospinal fluid replacement. Conclusion: This case demonstrates the association between Takotsubo syndrome and subarachnoid hemorrhage. When patients present with unexplained pulmonary edema with mild neurologic symptoms, clinicians should be alerted to subarachnoid hemorrhage and Takotsubo syndrome.