Nat Commun: All-drug affects breast cancer metastasis on animal models through the IL-6 pathway.

Surgery is one of the most commonly used treatments for solid organ tumors and is used for cancer prevention, diagnosis, determination of cancer staging and root removal. !----more than 80% of patients with malignant tumors receive at least one surgical treatment.However, in the case of malignant tumors such as triple-negative breast cancer, even if the tumor and its affected local areas are completely removed, the cancer will still recur or metastasis, becoming the leading cause of death.in recent years, a growing number of studies have shown that medication and treatment during surgery can lead to an increase in the number of tumor cells in the blood circulation and an increase in aggressive capacity.surgery also activates the neuroendocrine system to release a large number of immunosuppressive factors that lead to persistent cell-mediated immunosuppression.all of these factors contribute to the transfer of tumor cells to distant organs, which in turn affects the prognosis of cancer patients.anesthetics are the most commonly exposed drugs in surgery, and general anaesthetic drugs consist mainly of volatile anesthers such as heptafluoroetheride and intravenous anaesthetic sepsis such as propofol.a large retrospective study published in 2016 by Wigmore et al., analyzed the long-term (three-year) survival rates of more than 7,000 cancer patients after undergoing anaesthetic inhalation or intravenous anaesthetic surgery.after matching controls, the inhalation anaesthetic group and the intravenous anesthesia group were among 2607 patients (inhalation anesthesia group: 597 deaths, mortality 22.8%; intravenous anesthesiology group: 407 deaths, mortality 15.6%).multivariate analysis of known confounding factors in the matching group of the two anaesthetic sesorkats showed a significant increase in the risk of death in patients in the inhalation anaesthetic group (HR 1.46; 95% CI: 1.29-1.66), but other retrospective studies have concluded that anesthesia does not affect survival and tumor recurrence rates in cancer patients.recently, a large multicenter prospective study found that regional anaesthetic-analgesics (thoracic-propopiave compound, paravertebral blocks and propofol) did not reduce breast cancer recurrence after surgery compared to inhaled whole hemp-opioid analgesics (heptaflueeee ethers, general anesthesia with sevoflurane and opioid analgesia)., however, it is worth noting that the patients who were included in this study were primary breast cancer (phase 1 to 3), excluding patients with inflammatory breast cancer, without distinguishing between breast-preserving surgery and breast root removal.Given the diversity of patients and the complexity of breast cancer, local anaesthetic analgesia and intravenous anesthesia may be more beneficial to the prognosis of patients with malignant breast cancer.In addition, for breast cancer patients, the most common is the less traumatic breast-feeding surgery, so the strength of the body's stress response may also lead to differences in the results of the study.Although narcotic drugs have been used in modern medical treatment for more than a hundred years, there is very limited understanding of the mechanism of action of commonly used narcotic drugs such as heptafluorine and propofol, and little is known about the effects of narcotic drugs on tumor metastasis.so, Lin Jun, a professor at the State University of New York's Stony Brook School of Medicine, used mouse models to study the effects of different narcotic drugs on cancer metastasis and to further reveal its mechanisms.published in Nature Communications, entitled: Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse in mouse models (First Dr. Li Zhu, Dr. Huang). Theteam used two mouse models for tumor removal surgery to study the effects of different narcotic drugs: 4T1 congener transplanted mouse model (4T1 syngene mouse model) and human-derived trididum tumor cell MDA-MB-231 xenotransplantation (MDA-MB-231 xenograft model).in situ in both mouse models to inoculate tumor cells.when the in situ tumor grows to a certain size, simulated clinical surgery, under the action of different narcotic drugs, to remove the tumor in situ.then, after a period of observation, the tumor cell eventually assessed the transfer of tumor cells to the lungs.studies have shown a significant increase in postoperative pulmonary metablastomas in mice under the procedure for heptafluoroetherine than in mice that were anaesthetized with propofol.results were confirmed in two mouse models.in order to further reveal the mechanism of anaesthetic and to find potential targets to eliminate the effects of narcotic drugs in promoting tumor metastasis, they screened for changes in cytokine cytokines in blood and lung tissue shorter hours after surgery (i.e. three hours after surgery and one day after surgery).results showed an increase in the number of inflammatory cytokines associated with tumor metastasis in mice using heptafluoroetherthane as ananesthetic.re-use ELISA to further test for changes in IL-6 and VEGF to verify screening results.ELISA showed that three hours after surgery, the amount of IL-6 in the serum of the heptafluoroetheration group was significantly higher in mice in the propofol group.the day after surgery, the amount of IL-6 in the serum of the heptifflore ether group was twice that of the mice in the propofol group. There was no significant change in the amount of IL-6 inlung tissue.similar to il-6 results, the amount of VEGF in the serum of the heptafluoreloee group one day after surgery was higher than in the mice in the propofol group, but the change in VEGF was not as significant as that of IL-6.based on the above results and the important role of IL-6 in tumor metastasis, they further studied changes in il-6-related signaling pathways under the action of narcotic drugs.the activation of JAK kinases after the binding of IL-6 and its receptors, JAK kinases in turn catalyze the STAT3 protein (a transcription factor) bound on the receptor to produce phosphorylation modification, and the modified STAT3 protein enters the nucleus in the form of a dipolymer, binding with the target gene to promote cell growth and differentiation.in mice in the lung tissue of p-STAT3 (p-Tyr705) in the heptafluoretherane anaesthetic group were significantly higher than in mice in the propofol group within three hours to one day after surgery. to further confirm the role of the IL-6/JAK/STAT3 signaling pathway in the heptafluoroetheryl tumor metastasis process, a JAK kinase inhibitor AZD1480 was introduced into the 4T1 adhestyl transplanted mouse model. in this animal trial, mice began oral AZD1480 or its excipient as a control on the day of surgery, administering it daily after surgery until the end of the trial. AZD1480 significantly reduced the number of metastatic tumors in the lung tissue of the heptifflore anaesthetic group mice and reduced the level of p-STAT3 (p-Tyr705). The tumor microenvironment of lung tissue includes many different matrix cells (stroma cells), in which CD11b-myeloid cells effectively promotes the formation of microenvironments for cancer cell metastasis. in the 4T1 same-line transplanted mouse model, the lung tissue of the heptifluoroede anaesthetic group was found to have a significant increase in the lung tissue of the heptifflore anaesthetic group within one day after surgery compared to the propofol group. this phenomenon has also been confirmed in mDA-MB-231 xenotransplant models. In addition, the use of AZD1480 effectively reduces the immersion of CD11b-myeloid cells into lung tissue. concluded, heptafluoroetherine activates the IL-6/JAK/STAT3 signaling pathway during surgery by increasing the expression of IL-6 and induces CD11b-myeloid cells to accumulate in the lung tissue, thereby promoting the metastasis of tumor cells to the lungs. in contrast to direct effects on tumor cells, narcotic drugs mainly affect tumor metastasis by altering the tumor microenvironment, and this effect is performed under surgical trauma. different anesthetics have different effects on different types of tumors and even different subtypes of similar tumors, requiring a large number of prospective clinical studies to further confirm. at the same time, animal models are of great benefit to the study of the mechanism of anaesthetic drugs in tumor metastasis, and also provide reference for clinical drug selection, and find potential targets to overcome the side effects of narcotic drugs. .