Background: Metformin (MET) is a well-known anti-diabetic drug that also has anti-cancer effects. However, high therapeutic doses of MET on cancer cells and the low efficacy of combinatory therapeutic approaches limit its clinical application. Recent studies have shown that chrysin (CHR) can improve the pharmaceutical efficacy of MET by suppressing human telomerase reverse transcriptase (hTERT) and cyclin D1 gene expression. Objective: This study aimed to develop different ratios of methoxy poly(ethylene glycol)-b-poly(e-caprolactone) (MPEG-PCL) micelles for breast cancer to co-deliver a synergistic CHR/MET combination. Methods: CHR/MET drug-loaded micelles were prepared by modified thin-film hydration.Fourier infrared spectrum, gel permeation chromatography, transmission electron microscopy, and high-performance liquid chromatography were used to evaluate the physicochemical properties of nanostructures. Cell proliferation and cell apoptosis were assessed by MTT and Annexin V-FITC/PI double staining method. The gene expression of hTERT and cyclin D1 was measured by real-time PCR assay. A subcutaneous mouse T47D xenograft model was established to evaluate the in vivo efficiency. Results: When the ratio of MPEG-PCL was 1:1.7, the highest drug loading rate and encapsulation efficiency of CHR (11.31±0.37) and MET (12.22±0.44) were observed. Uniform MPEG-PCL micelles of 51.70±1.91 nm allowed MET to incorporate with CHR, which were co-delivered to breast cancer cells. We demonstrated that CHR/MET co-delivery micelles showed a good synergistic effect on inhibiting proliferation in T47D cells (combination index=0.87) by suppressing hTERT and cyclin D1 gene expression. Compared to the free CHR/MET group, the apoptosis rate on T47D cells by CHR/MET nano-micelles significantly improved from 71.33% to 79.25%. The tumour volume and tumour weight of the CHR/MET group increased more slowly than that of the single-drug treatment group (P<0.05). Compared to the CHR/MET group, the tumour volume and tumour weight of the CHR/MET nano-micelle group decreased by 42% and 59%, respectively. Conclusions: We demonstrated that ratiometric CHR/MET micelles could provide an effective technique for the treatment of breast cancer.

Purpose To examine the clinical significance of unoperated cervical cancer patients treated with different neoadjuvant chemotherapy (NACT) schemes followed by concurrent chemotherapy and radiotherapy (CCRT). Methods This retrospective analysis included women with locally advanced cervical cancer treated with NACT-CCRT between September 2011 and September 2014. Neoadjuvant chemotherapy included paclitaxel plus cisplatin (TP group; 62 patients) or paclitaxel plus loplatin (TL group; 58 patients), which were administered three weekly, and cisplatin or loplatin, which were administered weekly for synchronous chemotherapy. External beam radiation therapy (50.4–56.35 Gy/28 f, 180–215 cGy/f, 5 f/w) was followed by intracavitary brachytherapy (5 Gy per fraction, mostly 5 fractions, Ir192 based). Results One hundred twenty women were included in the analysis. The complete/partial response rate was 99.2% after treatment. The one-year, three-year, and five-year survival rates were 99.2%, 82.5%, and 70.8%, respectively. In the TP and TL groups, the three-year and five-year survival rates were 85.5% vs 77.6% and 75.8% vs 65.5%, respectively, with no significant difference. The 5-year overall survival (OS) rates between patients with stage IIB and stage IIIB disease were not significantly different (69.2% vs 64.7%). In the TP group, grade 3 or 4 digestive reactions were more frequent than those in the TL group. Leukopenia, neutropenia, and thrombocytopenia were more common in the TL group. No significant difference was found in anemia, radiation enteritis, radiation proctitis, or radiation cystitis between the groups. Conclusion Lobaplatin may be used as an alternative drug for patients with severe digestive system reactions or contraindications to cisplatin, but hematological toxicity must be considered, particularly in dose-intensive schemes. Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy (NACT-CCRT) warrants further prospective study in cervical cancer patients with a wide range of tumor invasion (eg, mass size ≥5 cm or stage IIIB).