TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.

OBJECTIVE: Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer. However, the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer (CRC) cells is unclear. This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells. METHODS: The expression of TOPK was detected in CRC tissues by immunohistochemistry, and the effect of TOPK knockdown was detected in CRC cells by Western blotting. CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells. Furthermore, proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy. DNA damage was detected by the comet assay. Changes in the DNA damage response signaling pathway were analyzed by Western blotting, and apoptosis was detected by flow cytometry. RESULTS: The expression of TOPK was significantly greater in CRC tissues at grades 2-4 than in those at grade 1. After irradiation, CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins, including phospho-cyclin-dependent kinase 1 (p-CDK1), phospho-ataxia telangiectasia-mutated (p-ATM), poly ADP-ribose polymerase (PARP), and meiotic recombination 11 homolog 1 (MRE11). CONCLUSIONS: TOPK was overexpressed in patients with moderately to poorly differentiated CRC. Moreover, TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.

Tank-mixing adjuvants enhanced the efficacy of fludioxonil on cucumber anthracnose by ameliorating the penetration ability of active ingredients on target interface.

In this study, pot and field experiments showed that S903, Hasten and Gemini-31511 can significantly enhanced the control efficacy of fludioxonil on cucumber anthracnose. Then by studying the deposition and penetration interaction between active ingredients and cucumber leaves to revealed how the adjuvants influence the interaction process between pesticide active ingredients and target plants to improve the control efficacy. By analysis the effect of fludioxonil deposition to synergism of adjuvants, indicated that fludioxonil active ingredient deposition caused by adjuvants was not the main factor for the adjuvants synergistic effect. Fludioxonil + S903 yielded the lowest surface tension and contact angle, which also implying the best wetting ability. The mean diameters in Hasten + fludioxonil group were much smaller than those in only fludioxonil group (5.39 µm-90 g a.i. ha-1, 5.50 µm-180 g a.i. ha-1), the average particle size only had 3.45 µm (90 g a.i. ha-1) and 3.94 µm (180 g a.i. ha-1). And the result of spray droplets was consistent with the particles of fludioxonil crystals observed on glass slides and cucumber leaves. Therefore, S903 improved the penetrability of fludioxonil in the target plants by improving the wetting and dispersion of active ingredients on the target interface. Meantime, Hasten improved the penetrability of fludioxonil in the target plants by decreasing the particle size of active ingredients.

Fungicide Formulations Influence Their Control Efficacy by Mediating Physicochemical Properties of Spray Dilutions and Their Interaction with Target Leaves.

In this study, three types of pyraclostrobin formulations (including emulsifiable concentrate (EC), suspension concentrate (SC), and microcapsules (MCs)) were used to control cucumber anthracnose. Pyraclostrobin EC had the highest inhibitory activity against Colletotrichum orbiculare in vitro. Much different from the bioactivity in vitro, pyraclostrobin MCs exhibited the highest control efficacy on cucumber anthracnose both in pot and field experiments. The physicochemical properties (particle size, surface tension) of the spray dilution, their interaction with target leaves (contact angle, adhesional tension, work of adhesion, retention, crystallization) and dissipation dynamic of the active ingredient were found to be highly potential factors that would significantly influence the control efficacy of pesticide formulations. Results showed that the control efficacies of different formulations of pyraclostrobin were determined mainly by the final behavior of the pesticides at the target interface, namely, the retention, crystallization, and dissipation dynamics of active ingredients. This study had revealed crucial factors that would influence the efficacy of different formulations of pyraclostrobin and thus could guide the rational and efficient use of different formulations of pesticides on target crops.