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http://anes.dxy.cn/bbs/topic/26040609
Isoflurane, a Commonly Used Volatile Anesthetic, Enhances Renal Cancer Growth and Malignant Potential via the Hypoxia-inducible Factor Cellular Signaling Pathway In Vitro.
What We Already Know about This Topic
? Hypoxia-inducible factor signaling is heavily implicated in cancer growth
? Enhancing the signaling of these transcription factors may increase metastatic potential
? Whether anesthetics exert promoting effects on cancer cells via modulation of this pathway remains uncertain
What This Article Tells Us That Is New
? Exposure of human renal cancer cells to isoflurane (0.5–2% for 2 h) resulted in up-regulation of levels of hypoxia-inducible factor-1α and -2α along with enhanced cell migration and cytoskeleton rearrangements
? Isoflurane promotes cancer cell growth and migration in vitro and hence enhances malignant potential
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DOI: 10.1097/ALN.0b013e31829e47fd
Benzonana, Laura L. B.Sc., M.Res., Ph.D. *; Perry, Nicholas J. S. M.B.B.S., B.Sc. +; Watts, Helena R. Ph.D. ++; Yang, Bob B.Sc. ; Perry, Iain A. B.Sc. ||; Coombes, Charles M.B.B.S. #; Takata, Masao M.D., Ph.D. **; Ma, Daqing M.D., Ph.D. ++
Miscellaneous
Background: Growing evidence indicates that perioperative factors, including choice of anesthetic, affect cancer recurrence after surgery although little is known about the effect of anesthetics on cancer cells themselves. Certain anesthetics are known to affect hypoxia cell signaling mechanisms in healthy cells by up-regulating hypoxia-inducible factors (HIFs). HIFs are also heavily implicated in tumorigenesis and high levels correlate with poor prognosis.
Methods: Renal cell carcinoma (RCC4) cells were exposed to isoflurane for 2h at various concentrations (0.5-2%). HIF-1[alpha], HIF-2[alpha], phospho-Akt, and vascular endothelial growth factor A levels were measured by immunoblotting at various time points (0-24h). Cell migration was measured across various components of extracellular matrix, and immunocytochemistry was used to analyze proliferation rate and cytoskeletal changes.
Results: Isoflurane up-regulated levels of HIF-1[alpha] and HIF-2[alpha] and intensified expression of vascular endothelial growth factor A. Exposed cultures contained significantly more cells (1.81 +/- 0.25 vs. 1.00 of control; P = 0.03) and actively proliferating cells (89.4 +/- 2.80 vs. 64.74 +/- 7.09% of control; P = 0.016) than controls. These effects were abrogated when cells were pretreated with the Akt inhibitor, LY294002. Exposed cells also exhibited greater migration on tissue culture-coated (F = 16.89; P = 0.0008), collagen-coated (F = 20.99; P = 0.0003), and fibronectin-coated wells (F = 8.21; P = 0.011) as along with dramatic cytoskeletal rearrangement, with changes to both filamentous actin and [alpha]-tubulin.
Conclusions: These results provide evidence that a frequently used anesthetic can exert a protumorigenic effect on a human cancer cell line. This may represent an important contributory factor to high recurrence rates observed after surgery.
(C) 2013 American Society of Anesthesiologists, Inc.
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Cancer Prognosis : Can Anesthesia Play a Role?
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-----------------------------Collectively, these findings suggest that isoflurane could promote a cellular mechanism (HIFs), which is implicated
in tumorigenesis, and isoflurane might enhance the cellular activities that are associated with a malignant phenotype in
the cells. Note that isoflurane has been shown to induce cell death, rather than increase growth of cells, in other studies.Therefore, as suggested by other studies, it is possible that isoflurane may have a dual effect on cell death, which is dependent on specific cell lines, various treatment time, and different concentrations.16,17
Nevertheless, the well designed and wellperformed study by Dr. Daqing Ma’s group is a timely and welcome startingpoint, grounded in sound and reasoned biochemistry at the cellular level, which could direct and focus the endeavors of much-needed in vivo and clinical follow-up work. The clinical evidence on the subject is limited to small-scale, often
retrospective studies and is, at times, conflicting, with regard to how true or sizeable this concern is or how much of a
difference that an anesthetic technique can make toward a patients’ long-term disease-free survival. Of course, what is
sorely missing at this moment is a good number of randomized controlled trials that have adequate power and followup, but such are the number of variables in the perioperative period and such is the heterogeneity of “cancer” as a disease that accounting for each of these will be a difficult and costly challenge. Basic science studies such as the one by Benzonana et al. published in the current issue of Anesthesiology are essential for more in vitro and in vivo studies with different cancer cell lines and different anesthetics to be launched in this field. The current and future research findings would ultimately help to design clinical trials to explore good anesthetics/ anesthetic technique for cancer patients.
Zhongcong Xie, M.D., Ph.D.,
Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts. [email protected]
Cancer Prognosis.pdf(331.03k) 在线查看
wdhk wrote:
1842年，美国的乡村，Long实施了人类第一例事实存在的乙醚麻醉；
1846年，美国麻省总院，Morton实施了人类第一例公开报道的乙醚麻醉；
作为现代外科学发展三大里程碑之一的麻醉，尤其是神奇的全麻，依然还披着神秘的面纱。
这个曾让医学界为之兴奋的全身麻醉，在近5年却悄然背负上了中枢神经毒性的标签；如今，也有其促肿瘤的效应。
尽管全世界的麻醉医生，愿意听到，我们给病人提供的麻醉，是保护的。但是，事实如何？期待更有说服力的在体研究，临床流调。 |
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发表于 2013-8-4 18:14:51
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