Trastuzumab has led to a marked improvement in the outcomes of patients with human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. However, the effects of trastuzumab on HER-2-positive breast cancer are limited by the emergence of its cardiotoxicside effects. MicroRNA (miR)-135b-5p has been shown to inhibit tumor metastasis in breast cancer. The present study aimed to explore the effects of miR-135b-5p overexpression on the efficacy of trastuzumab in HER-2-positive breast cancer. Reverse transcription-quantitative PcR was performed to detect the levels of miR-135b-5p. cell viability was evaluated with a cell counting Kit-8 assay. Annexin V/propidium iodide staining was employed to detect the number of apoptotic cells. Flow cytometry assay was performed to investigate the cell cycle. Western blotting was used to detect the expression levels of Bax, cleaved caspase-3, Bcl-2, cyclin d2, p27 Kip1 and cyclin E1. cell migration and invasion were detected by Transwell assay. Luciferase assays were conducted to identify the target gene of miR-135b-5p. In addition, an in vivo tumor xenograft model was established. miR-135b-5p agomir significantly enhanced the anti-proliferative effect of trastuzumab on HER-2-positive breast cancer cells via the induction of apoptosis, whereas the anti-metastatic effect of trastuzumab was enhanced by miR-135b-5p agomir treatment. Subsequently, luciferase assays indicated that cyclin d2 was the direct target of miR-135b-5p, whereas overexpression of the latter arrested cell cycleduring the G 0 /G 1 phase. Moreover, miR-135b-5p agomir notably increased the antitumor effect of trastuzumab in vivo. The data demonstrated that miR-135b-5p sensitized HER-2-positive breast cancer cells to trastuzumab in vitro and in vivo by directly binding to cyclin d2. These results suggested that the combination of miR-135b-5p with trastuzumab may be a therapeutic strategy for patients with HER-2-positive breast cancer.

Anaplastic thyroid cancer (ATC) represents the most aggressive subtype of thyroid cancer and has a poor prognosis. In addition to surgery, chemotherapy is an important treatment for ATC; however, the therapeutic effects of current chemotherapies for ATC are not particularly promising. There is a high proportion of side population (SP) cells in ATC, which may be a reason for its drug resistance. In the present study, the antitumor activities of combined octreotide (OCT) and cisplatin (DDP) on the proliferation and apoptosis of ATC SP cells were evaluated. First, SP cells from 8305C and BHT101 cell lines were detected and sorted. Following culture for 1 week, cluster of differentiation (CD)44, CD133, ATP-binding cassette (ABC) subfamily B member 1 (ABCB1), ABC subfamily G member 2 (ABCG2) and somatostatin receptor expression was detected to characterize the SP cells. An MTT assay was performed to investigate the combined effects on 8305C-SP cell proliferation, and a mouse model was used to investigate the combined effects on 8305C-SP cell proliferation . Annexin V/propidium iodide staining was used to investigate the combined effects on 8305C-SP cell apoptosis. Chemotherapeutic drug resistance-associated protein expression and apoptosis-associated protein expression were also detected following combined treatment. As a result, SP cells were identified in 8305C and BHT101 cells, and the proportion of 8305C-SP cells was increased compared with that of BTH101-SP cells. SP cells have enhanced proliferation, tumorigenicity and drug resistance compared with main population cells. The combined treatment of OCT with DDP suppressed the proliferation of 8305C-SP cells and , and induced 8305C-SP cell apoptosis. Combined treatment decreased the ABCB1 and ABCG2 expression by SP cells and activated mitochondrial apoptotic signaling, resulting in cell apoptosis. In conclusion, these data support the hypothesis that combined treatment with OCT and DDP induces ATC cell apoptosis and suppresses cell proliferation. These data provide a theoretical basis for further combined chemotherapy clinical applications.