Sulfasalazine increases the radiosensitivity of colorectal cancer cells by promoting ferroptosis / 中华放射肿瘤学杂志

Objective:To investigate the radiosensitization effect of low-dose sulfasalazine (SAS) on colorectal cancer (CRC) cells.Methods:Proliferation inhibition effect of SAS on CRC cells was detected by CCK-8 assay, and the concentration of SAS in vitro assays was based on its IC10 value. CRC cells were treated with SAS alone or combined with inhibitors of apoptosis, autophagy, ferroptosis and necroptosis, then cell viability was detected by CCK-8 assay. Trypan blue staining, clone formation assay and cell growth curves were used to verify the radiosensitization effect of SAS on CRC cells in vitro. CRC cells were treated with SAS and radiotherapy, then the intracellular contents of lipid peroxidation and the protein levels of GPX4, PTGS2, cleaved PARP and active caspase 3 were evaluated, respectively. Subcutaneous xenograft tumor mouse model was established to further verify the radiosensitization effect of SAS in vivo. Results:High dose (lethal dose) of SAS could induce apoptosis and ferroptosis in CRC cells. Low dose (non-lethal dose) of SAS enhanced the radiosensitivity of CRC cells in vitro, and the radiosensitivity effect of SAS could only be abolished by ferroptosis inhibitor (Fer-1). Low dose of SAS combined with radiotherapy significantly down-regulated the expression of GPX4, whereas increased the intracellular lipid peroxidation levels and the expression of PTGS2. SAS also showed significant radiosensitization effect in subcutaneous xenograft tumor model. Conclusion:Our findings suggest that low-dose SAS could increase the radiosensitivity of CRC cells by promoting ferroptosis.

Expression and significance of long non-coding RNA RP11-629B11.4 in triple negative breast cancer patients / 国际肿瘤学杂志

Objective To investigate the expression and clinical significance of long non-coding RNA (lncRNA) RP11-629B11.4 in triple negative breast cancer (TNBC) patients.Methods The expression of lncRNA RP11-629B11.4 was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) in TNBC tissues (n =45) and non triple negative breast cancer (N-TNBC,n =89) to analyze the relationship between the expression of lncRNA RP11-629B11.4 and the prognosis of patients.Results The expression of lncRNA RP1 1-629B11.4 in TNBC tissues was 7.805 ± 0.538,significantly higher than that in N-TNBC tissues (1.637 ± 0.409,t =21.460,P ＜ 0.001).The expression of lncRNA RP11-629B11.4 in the TNBC patients was related with histological grade (x2 =7.540,P =0.040),clinical stage (x2 =9.858,P =0.007),lymph node metastasis (x2 =4.388,P =0.036) and Ki-67 expression (x2 =7.872,P =0.005).In the N-TNBC group,there was no significant correlation between the expression of lncRNA RP11-629B11.4 and clinicopathological characteristics (all P ＞ 0.050).The progression free survival time of TNBC patients with higher expression of lncRNA RP11-629B11.4 was (15.90 ±2.76) months,shorter than that of patients with lower expression (26.62 ± 3.80) months,with a statistically significant difference (x2 =49.750,P ＜ 0.001).The overall survival time of TNBC patients with lower expression of lncRNA RP11-629B11.4 was (38.84 ±3.55) months,significantly longer than that of patients with higher expression [(24.69 ± 3.50) months],with a statistically significant difference (x2 =50.730,P ＜ 0.001).Cox regression model analysis showed that lymph node metastasis (HR =1.980,P =0.019),the expression of lncRNA RP11-629 B11.4 (HR =4.030,P ＜ 0.001) clinical stage (HR =2.670,P =0.008) and were independent prognostic factors in patients with TNBC.Conclusion The lncRNA RP11-629B11.4 is over-expressed in TNBC.lncRNA RP11-629B11.4 may be involved in the regulation of TNBC,and it may be used as a potential target for evaluating the prognosis of TNBC.

[Role and clinical significance of RLIP76 in regulation of multi-drug resistance of small cell lung cancer].

OBJECTIVE: To investigate the role of RLIP76 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to analyze the relationship between its expression and prognosis. METHODS: The expressions of RLIP76 protein and gene were detected by Western blotting and real-time PCR (RT-PCR) in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively. siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression. The drug-sensitivity of cells to chemotherapeutic drugs (ADM, DDP, VP-16) were detected by CCK8 assay. The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry. The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed. RESULTS: The expression of RLIP76 in H69AR cells was 13.675 ± 0.983, significantly higher than 1.074 ± 0.107 in the H69 cells (P < 0.01). The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated (P< 0.001). The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression (P = 0.003). The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively (P < 0.01). The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients (P < 0.05). CONCLUSIONS: Our results suggest that RLIP76 is involved in the regulation of small cell lung cancer multidrug resistance. RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

Clinical Effect of Skeletal Metastases Treated by Chemotherapy Combined with Ibandronate / 药物流行病学杂志

Objective:To observe the therapeutic effect of the treatment with intravenous(Ⅳ)ibandronate com- bined with chemotherapy on patients with skeletal metastases.Method:138 patients with skeletal metastases were randomly divided into ibandronate group combined with chemotherapy(68 cases)and simple chemotherapy group(70 cases).The controlled group took a standard chemotherapy project but combined the treatment group took a chemotherapy project plus ibandronate.In a week after the chemotherapy,68 cases of the treatment group were treated with ibandronate 4mg in NS 500ml by intravenous infusion once 4 weeks for 3 months.The effect was evaluated when the three cycles finished.Result: There was a statistical difference(P

Irirotecan Combined with Fluoropyrimidine in the Treatment of 46 Cases with Metastatic Colorectal Carcinoma / 药物流行病学杂志

Objective:To evaluate the efficacy and toxicity of Irirotecan(CPT-11) combined with 5-FU/CF in the treatment of metastatic colorectal cancer, in which FOLFOX4 or LV5FU2 had failed to cure it. Method: 46 cases of metastatic colorectal cancer patients were treated by CPT-11 combined with 5-FU/CF for one cycle every two weeks; namely, CPT-11 was given by 180mg/m2 iv d1, CF by 200mg/m2 iv d1-2, 5-FU by 400mg iv bolus d1, and 5-FU by 600mg/m2 iv 22h d1-2. Two weeks was a cycle. The study term was 3-6 months. Result:CR was 0, PR was 39. 13% (18/46) , SD was 43.47% (20/46) , PD was 17.39% (8/46) and CBR was 82.69% (38/46). The clinical reaction evaluation efficiency was 78. 86% (36/46). Their life quality was notably improved. Conclusion:CPT-11 combined 5-Fu/CF can be used as second-line treatment for metastatic colotedal cancer.