Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1.

Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues. Using both overexpression and knockdown of COX-2, we demonstrated that the localization of COX-2 at mitochondria promotes the stemness of NPC by recruiting the mitochondrial translocation of p53, increasing the activity of Drp1 and inducing mitochondrial fisson. Inhibition of the expression or the activity of Drp1 by siRNA or Mdivi-1 downregulates the stemness of NPC. The present study also found that inhibition of mitochondrial COX-2 with resveratrol (RSV), a natural phytochemical, increased the sensitivity of NPC to 5-fluorouracil (5-FU), a classical chemotherapy drug for NPC. The underlying mechanism is that RSV suppresses mitochondrial COX-2, thereby reducing NPC stemness by inhibiting Drp1 activity as demonstrated in both the in vitro and the in vivo studies. Taken together, the results of this study suggest that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC.

[Changes of historical Paragonimus metacercaria infection rates of freshwater crabs in Yongjia County].

OBJECTIVE: To understand the changes of Paragonimus metacercaria infection rates of freshwater crabs in Paragonimus endemic areas and explore the causes in Yongjia County, Zhejiang Province, China. METHODS: A field investigation was carried out. The freshwater crabs were collected and the metacercaria were separated from the crabs. The infection rates, infectiosities and infection indexes were calculated and the results were vertically compared with the historical findings. The causes of the changes were discussed. RESULTS: Compared with those in 1980, the average infection rate in original endemic areas decreased from 59.71% to 21.50% (P < 0.05), while the infection density decreased from 1.09/g to 0.23/g (P < 0.05). The infection index decreased obviously. In Hesheng Village, it decreased from 4.05 to 0.01 (P < 0.01), in Wuchi Village, it was from 37.90 to 2.91 (P <0.01), and in Daruoyan Scinic area,it was from 5.85 to 0.03 (P < 0.01). Two endemic areas disappeared but two new endemic areas (Sihai Village and Sunshan Village) were found, and in Sunshan Village, the metacercaria infection rate was 100%, the infection density and infection index were 21.30/g and 3 402.68 respectively, which meant it was a super high endemic focus. CONCLUSION: The Paragonimus metacercaria infection rate in crabs is lower than before in Yongjia County, but some super high epidemic focus of paragonimiasis still exists. Therefore, we still should strengthen the control measures.