Application of the platinum-based chemotherapy for colorectal cancer is restricted due to its severe cytotoxic effects. In this study we used synergistic strategies by combining (-)-Epigallocatechin gallate (EGCG) with cisplatin or oxaliplatin to minimize the ill effects of platinum-based therapy. MTS assay was used to examine the effect of EGCG, cisplatin and oxaliplatin on the proliferation of human colorectal cancer DLD-1 and HT-29 cells. Autophagic process was evaluated by detection of LC3-II protein, autophagosome formation, and quantification of Acidic Vesicular. Treatment of DLD-1 and HT-29 cells with EGCG plus cisplatin or oxaliplatin showed a synergistic effect on inhibition of cell proliferation and induction of cell death. EGCG enhanced the effect of cisplatin and oxaliplatin-induced autophagy in DLD-1 and HT-29 cells, as characterized by the accumulation of LC3-II protein, the increase of acidic vesicular organelles (AVOs), and the formation of autophagosome. In addition, transfection of DLD-1 and HT-29 cells with siRNA against ATG genes reduced EGCG synergistic effect. Our findings suggest that combining EGCG with cisplatin or oxaliplatin could potentiate the cytotoxicity of cisplatin and oxaliplatin in colorectal cancer cells through autophagy related pathway.

Recurrent radiation-associated leiomyosarcoma after postoperative radiotherapy for breast invasive ductal carcinoma: a case report and literature review Wei Zhang, Xinlan Qu, Yuan Fang

Background: Preterm birth is a major cause of perinatal mortality and complications, with inflammation being a key contributing factor. Current treatments, like uterine contraction inhibitors and antibiotics, are unsatisfactory. Aspirin, a cyclooxygenase inhibitor, shows promise in treating infectious preterm labor but has limited in vivo studies and an unclear mechanism. Methods: In this study, a mouse model of infectious preterm birth was established via lipopolysaccharide (LPS) injection, and the aspirin doses used in these animals were converted from the recommended human doses by the body surface area method, with the high-dose and low-dose groups set at 0.78 mg/kg and 0.21 mg/kg, respectively. ELISA detected inflammatory factors TNF-α, IL-1β, IL-6 in serum, amniotic fluid and placenta. WST-8 kit and TBA method measured serum SOD activity and MDA content, respectively. DTNB colorimetric method analyzed glutathione content in liver and placenta. Western blot detected MyD88, IκB, p-IκB and nucleus NF-κB p65 protein expression in uterine tissues. Results: Results showed the 75 μg/kg LPS group had a 91.7% preterm birth rate and 4.67% stillbirth rate. Low-dose (66.7%) and high-dose (41.6%) aspirin reduced preterm birth and increased live birth rates, with significant intergroup differences (P < 0.05). Aspirin lowered LPS-induced TNF-α, IL-1β, IL-6 in serum, amniotic fluid and placenta, regulated oxidative stress, reversed MyD88/p-IκB overexpression and reduced p65 nuclear translocation. TLR4/NF-κB inhibitors downregulated these factors and nuclear NF-κB p65/p-IκB. Additionally, we found that inflammatory LPS induced abnormal fetal mouse skeletal development (e.g., malformation and deficiency), which was ameliorated by aspirin exposure. Conclusion: Aspirin may ameliorate preterm birth by up-regulating TLR4/NF-κB pathway, laying theoretical basis for aspirin clinical application in preterm birth.