Long-chain non-coding RNA MALAT1 regulates paclitaxel resistance of breast cancer cells by targeting miR-485-3p / 南方医科大学学报

OBJECTIVE@#To investigate the role of long-chain non-coding RNA MALAT1 in modulating paclitaxel resistance in breast cancer cells.@*METHODS@#Breast cancer SK-BR-3 cells were treated with gradient concentrations of paclitaxel to induce paclitaxel resistance of the cells. The resistant cells were transfected with si-NC, si-MALAT1, pcDNA, pcDNA-MALAT1, miRNC, miR-485-3p mimics, si-MALAT1+anti-miR-NC, or si-MALAT1+anti-miR-485-3p liposomes. Following the transfections, the cells were examined for changes in IC of paclitaxel using MTT assay; the protein expression of P-gp, Bcl-2 and Bax were detected with Western blotting, and a dual luciferase reporter assay was used to detect the binding of MALAT1 to miR-485-3p.@*RESULTS@#Compared with paclitaxel-sensitive SK-BR-3 cells, paclitaxel-resistant SK-BR-3 cells showed significantly increased the IC of paclitaxel with up-regulated MALAT1 expression and down-regulated miR-485-3p expression ( < 0.05). Silencing MALAT1 or overexpressing miR-485-3p obviously lowered the IC of paclitaxel and the expression of P-gp and Bcl-2 and increased the expression of Bax in SK-BR-3/PR cells ( < 0.05). miR-485-3p was identified as the target of MALAT1, and inhibiting miR-485-3p significantly reverse the effect of MALAT1 silencing on IC of paclitaxel and the expressions of P-gp, Bcl-2 and Bax in SK-BR-3/PR cells ( < 0.05).@*CONCLUSIONS@#MALAT1 can modulate paclitaxel resistance in breast cancer cells possibly by targeting miR-485-3p to down-regulate P-gp and Bcl-2 and up-regulate Bax.

The necessity of EGFR-targeted therapy combined with synchronized whole brain radiotherapy for non-small-cell lung cancer with mutated EGFR and brain metastasis / 中华放射肿瘤学杂志

Objective To explore the necessity of EGFR?targeted therapy combined with synchronized whole brain radiotherapy ( WBRT ) for non?small?cell lung cancer ( NSCLC ) with mutated EGFR and brain metastasis by comparing the effects on prognosis between WBRT combined with tyrosine kinase inhibitor ( TKI) and TKI alone. Methods A retrospective analysis was performed in 43 patients with EGFR mutation?positive NSCLC and brain metastasis. In those patients, 24 patients received WBRT plus TKI and 19 patients TKI alone. Results The overall response rate ( RR) and 6?month intracranial disease control rate ( CR) were significantly higher in the WBRT+TKI group than in the TKI group ( 79% vs. 37%, P=0. 002;79% vs. 63%, P=0. 008). The median intracranial progression?free survival (IPFS) time was significantly longer in the WBRT+TKI group than in the TKI group ( 23. 7 vs. 8. 3 months, P=0. 025) . The multivariate analysis indicated that the control of lung cancer, WBRT+TKI, and single brain metastasis were favorable factors for substantially longer IPFS time ( P=0. 033,0. 019,0. 019) . In 23 patients with exon 19 deletion, 12 patients received WBRT+TKI and 11 patients TKI alone;compared with the TKI group, the WBRT+TKI group had significantly higher RR and 6?month CR as well as significantly longer IPFS ( 100%vs. 35%, P=0. 000;100% vs. 55%, P=0. 008;23. 7 vs. 8. 4 months, P=0. 003). In 20 patients without exon 19 deletion, however, there were no significant differences in RR or 6?month CR between the WBRT+TKI group (n=12) and the TKI group (n=8)(64% vs. 50%, P=1. 000;58% vs. 75%, P=0. 642).The median IPFS was 14. 4 and 8. 4 months ( P=0. 864) . Conclusions WBRT combined with TKI is superior to TKI alone in the treatment of NSCLC with brain metastasis. Patients with exon 19 deletion have substantially better treatment outcomes.