Morphine Promotes the Angiogenesis of Postoperative Recurrent Tumors and Metastasis of Dormant Breast Cancer Cells

吗啡促进术后复发肿瘤的血管生成和休眠乳腺癌细胞的转移

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作者:Shi Cheng, Mingyan Guo, Zhongqi Liu, Yanni Fu, Haixuan Wu, Chengli Wang, Minghui Cao

Background

Surgery plays a significant role in the comprehensive treatment of breast cancer, and opioids are often the first-choice analgesics in the perioperative period. However, recent studies showed that opioids may enhance the angiogenesis of breast cancer and the recurrence and metastasis of tumor cells. Objectives: We

Conclusion

In the current study, we found that morphine promotes the angiogenesis of the recurrent postoperative tumors of nude mice with breast cancer and the proliferation of tumor cells and such promotion may be related to the PI3K-c-Myc signaling pathway.

Methods

Forty female nude mice with breast tumor were randomly divided into 4 groups (n = 10). They were treated with (i) normal saline (10 mL/kg), (ii) morphine (10 mg/kg), (iii) morphine plus naloxone (10 + 4 mg/kg), and (iv) naloxone (4 mg/kg) for 2 weeks. Four groups of MDA-MB-231 cells were administered (i) Dulbecco's Modified Eagle's Medium, (ii) morphine (10 μmol/mL), (iii) morphine plus naloxone (10 + 10 μmol/mL), and (iv) naloxone (10 μmol/mL). The influence of morphine in each treated group was evaluated by immunocytochemistry and Western blotting.

Results

Mice in the morphine group had higher rates of Ki67-positive cells, lower rates of apoptotic index, and a significant increase in the microvessels density of the tumor as evidenced by CD31 staining (p < 0.05). Furthermore, the MDA-MB-231 cells in the morphine group showed an increase in p-Akt, c-Myc, and thrombosponin-1 expression.

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