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【medical-news】研究显示给小鼠注射维C促使肿瘤缩
http://www.medicalnewstoday.com/articles/117494.php
US researchers found that giving mice with rapidly spreading ovarian, pancreatic, and brain cancers high "pharmacologic " dose injections of vitamin C, also known as ascorbate or ascorbic acid, caused the tumors to shrink and their growth to slow down by as much as 50 per cent.
The study was the work of researchers at the US National Institutes of Health (NIH) and was published online ahead of print on 4th August in the Proceedings of the National Academy of Sciences, PNAS.
Vitamin C is an essential nutrient that is commonly regarded as an antioxidant, wrote the researchers. But in this study, using 43 cancer and 5 normal cell lines in the laboratory, they showed that at high pharmacologic doses it behaved like a a prooxidant, generating hydrogen peroxide and producing an anticancer effect that killed up to 75 per cent of cancer cells without adversely affecting normal cells.
Then they tested the effect in mice, using injections to achieve the high pharmacologic doses in order to bypass the digestive system which caps the amount of vitamin C allowed into the bloodstream. Using real time microdialysis sampling in mice with grafted glioblastoma (brain cancer) tumors, they showed that a single pharmacologic dose of vitamin C sustained the same prooxidant effect, including generation of hydrogen peroxide, inside the tumors (in the interstitial fluid surrounding the cancer cells) but not in the bloodstream.
Finally, the researchers gave immune-deficient mice with grafted ovarian, pancreatic and glioblastoma tumors daily injections of vitamin C and found it significantly reduced tumor growth and weight by 41 to 53 per cent (with p values of <0.005, 0.05 and 0.001 for each cancer type respectively). Also, in 30 percent of the mice with glioblastoma that did not have the vitamin C injections, the cancer had spread to other organs, but there were no signs of cancer spreading to other organs in the mice treated with vitamin C.
The researchers also showed it was possible to achieve similar pharmacologic concentrations intravenously in humans, although they did not test the effect on tumors in humans.
They concluded that:
"These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options."
The researchers decided to revisit the effect of vitamin C on cancer because although previous studies had examined it, they had not looked further into the intravenous dose, only the oral dose. But the problem with the oral dose is that the digestive system intervenes to cap the amount of vitamin C allowed into the bloodstream.
"When you eat foods containing more than 200 milligrams of vitamin C a day -- for example, 2 oranges and a serving of broccoli -- your body prevents blood levels of ascorbate from exceeding a narrow range," said Dr Mark Levine, M.D, lead author and chief of the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH.
To bypass the body's natural controls, Levine, accompanied by colleagues from the NIDDK and the National Cancer Institute (NCI), both components of the NIH, as well as the University of Kansas, injected vitamin C directly into the veins or abdominal cavities of the mice. By doing so, they could deliver high doses, up to 4 grams per kilogram of body weight daily.
"At these high injected doses, we hoped to see drug-like activity that might be useful in cancer treatment," said Levine.
Vitamin C is an essential dietary component that plays an important health-giving role, and prolonged lack of the vitamin results in scurvy and eventually death. It helps many enzymes to do their job, and scientists believe it also acts as an antioxidant that protects cells from being damaged by free radicals. But in this study, at high doses, the vitamin appeared to behave like a a prooxidant, attacking instead of protecting cells, in this case cancer cells.
Levine explained why the NIH team decided to revisit vitamin C as a potential cancer treatment:
"Clinical and pharmacokinetic studies conducted in the past 12 years showed that oral ascorbate levels in plasma and tissue are tightly controlled. In the case series, ascorbate was given orally and intravenously, but in the trials ascorbate was just given orally. It was not realized at the time that only injected ascorbate might deliver the concentrations needed to see an anti-tumor effect."
Levine said there are plans to trial vitamin C as a pharmacological cancer treatment in humans.
"Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice."
Qi Chen, Michael Graham Espey, Andrew Y. Sun, Chaya Pooput, Kenneth L. Kirk, Murali C. Krishna, Deena Beneda Khosh, Jeanne Drisko, and Mark Levine.
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作者:admin@医学,生命科学 2011-04-07 18:33
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