ABSTRACT
In this study, we have aimed to prepare folic acid-conjugated dextran stearate (DF) polymeric micelles to target resveratrol in lung cancers. The polymeric micelle was nanosized and exhibited a controlled drug release pattern. The resveratrol (RSV)-loaded dextran stearate (RSV-DF) micelles exhibited an enhanced cellular uptake in A549 cells due to the folic acid-based receptor interactions. We have demonstrated that RSV-DF polymeric micelles retain the cytotoxic and metabolic effects of RSV on A549 cancer cells with potencies similar to that of the free compound. Furthermore, RSV-DF showed an enhanced cellular apoptosis of cancer cells compared to that of free RSV. We have found that apoptosis induced by RSV-DF was associated with the higher expression of p53, caspase-3, and BAX than the free RSV. The higher level of BAX and caspase-3 further indicates the involvement of mitochondria-dependent apoptosis in the anticancer efficacy of formulations. Based on these results, it can be concluded that natural compound like RSV could be an interesting prospect to treat lung cancers and the fact that folic acid-conjugated dextran stearate could be a potential carrier to deliver the drug in the cancer cells.
Subject(s)
Dextrans/chemistry , Folic Acid/chemistry , Stilbenes/chemistry , A549 Cells , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Caspase 3/metabolism , Drug Liberation , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mitochondria/drug effects , Mitochondria/metabolism , Particle Size , Resveratrol , Stilbenes/toxicity , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
OBJECTIVE: To determine the preoperative serum VEGF, IL-6, and CRP levels in colorectal carcinoma, and to explore their correlation with disease status and prognosis. METHODS: Serum VEGF and IL-6 levels were assessed using ELISA, and CRP was measured by immunoturbidimetry. They were compared between the colorectal carcinoma group and the control group. The five-year survival rate and poor prognostic factors were analyzed by Kaplan-Meier and Log-rank method, respectively. RESULTS: The serum VEGF, IL-6, and CRP levels in colorectal carcinoma were (591 ± 312) pg/ml, (13.2 ± 3.7) pg/ml, and (1.14 ± 0.87) mg/dl, respectively, higher than that in the control group. The two groups showed significant difference in VEGF and CRP (P < 0.001, P = 0.002). VEGF expression was higher in male than that in female [(638 ± 387) pg/ml vs. (552 ± 271) pg/ml, P = 0.042]. The cases with tumor size smaller than 5 cm had lower VEGF expression compared with that in cases with tumor size ≥ 5 cm [(538 ± 275) pg/ml vs. (647 ± 331) pg/ml, P = 0.009]. IL-6 expression showed significant difference in males (11.7 ± 3.2) and females (15.2 ± 4.0) pg/ml, (P = 0.011). The five-year survival rate in the group with VEGF < 591 pg/ml was 86.8% (33/38), higher than that in the ≥ 591 pg/m group. High VEGF level tended to reduce survival (χ(2) = 0.933, P = 0.344). VEGF ≥ 591 pg/ml was a factor of poor prognosis in colorectal carcinoma, assessed by Log-rank methods (P < 0.05). Tumor size and VEGF concentration were risk factors of prognosis (P = 0.032, OR = 0.985; P = 0.011, OR = 0.976). CONCLUSIONS: Serum VEGF and IL-6 expressions have gender differences. Serum VEGF can be used as a biomaker of clinical diagnosis of colorectal cancer, and has an important significance on the prognosis of patients.
