Multiple drug resistance remains an unsolved problem in cancer therapy. A previous study has demonstrated that the chemotherapeutic drug doxorubicin (Dox) induced upregulation of P-glycoprotein in endothelial cells, resulting in a 20-fold increase in drug resistance and reduced efficiency of doxorubicin treatment in a mouse tumor model. In the present study, the cross-resistance and sensitivity of HMECd1 and HMECd2 established cell lines to anti-angiogenic drugs, particularly sunitinib, was explored. The results revealed that Dox treatment induced a significant increase in the breast cancer resistance protein (ABCG2) gene transcription and protein expression. This increase gave rise to a 4- to 5-fold increase in the half maximal inhibitory concentration of the HMECd1 and HMECd2 cells in response to sunitinib treatment in vitro. Functionally, the role of ABCG2 in the resistance to sunitinib was confirmed by the use of the ABCG2 inhibitors fumitremorgin C and diethylstilbestrol, which blocked cell resistance. The present study indicates that endothelial cells exhibit cross-resistance between cytotoxic drugs and anti-angiogenic drugs. This suggests that multiple drug resistance induced by chemotherapy in endothelial cells may affect the efficiency of anti-angiogenic drugs.

Sphingosine kinase 1 (SPHK1), an ATP-dependent protein, has previously been demonstrated to be upregulated in several types of human cancer and to play an important role in tumor development and progression. However, the role of SPHK1 in predicting long-term prognosis in patients with papillary thyroid carcinoma (PTC) remains unclear. The purpose of the present study was to assess the significance of SPHK1 expression and its associations with clinicopathological characteristics and prognostic outcome in patients with PTC. Immunohistochemistry staining was retrospectively performed to investigate the expression levels of SPHK1 in 92 PTC tumors. Statistical analyses revealed that high levels of SPHK1 expression were associated with tumor size, lymph node metastasis and the Tumor-Node-Metastasis stage. The disease-free survival (DFS) time of patients that exhibited high levels of SPHK1 expression was shorter, whereas patients with lower levels of SPHK1 expression survived longer. Furthermore, multivariate analysis suggested that upregulated SPHK1 was an independent prognostic factor for predicting DFS of patients with PTC. The results of the Cell Counting Kit-8 and invasion assays demonstrated that SPHK1 overexpression significantly enhanced the proliferation and invasion of a PTC cell line, consistent with clinical findings. The results from the present study provide evidence that elevated expression levels of SPHK1 may be involved in the development and progression of PTC, indicating that this protein may act as a potential prognostic marker for patients with this disease.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick sensor involved in the base excision repair (BER) pathway. Olaparib, a PARP inhibitor, has demonstrated antitumor activity in homologous recombination (HR)-deficient cancers. To extend this specific therapy to other types of carcinomas, a panel of 11 different cancer cells were screened in the present study. JF-305, a pancreatic cancer cell line of Chinese origin, demonstrated sensitivity to the PARP inhibitor 6(5H)-phenanthridinone. In the present study, 3 μM olaparib conferred a cell survival rate of 25% following four days of treatment. The colony formation efficiency was 83% at 10 nM, and dropped to 12% at 1 μM following seven days of treatment. Furthermore, olaparib induced cell cycle arrest in the S and G2/M phases prior to the initiation of apoptosis. Although the incidence of double-strand breaks (DSBs) was increased in the olaparib-treated JF-305 cells, the RAD51 foci were well formed at the sites of γ-H2AX recruitment, indicating an activated HR mechanism. Furthermore, tumor growth was reduced by 49.8% following 22 days of consecutive administration of 10 mg/kg olaparib in the JF-305 xenograft mouse model. In summary, the JF-305 cell line was sensitive to olaparib and provided a prospective model for the preclinical assessment of PARP inhibitors in the therapy of pancreatic cancer.