Prevention of colorectal cancer development by Bio-K+ probiotic formula

结肠癌是发病率和死亡率的主要原因之一，不仅在西方工业化国家，在亚洲发达国家也是如此。目前，结直肠癌（CRC）是加拿大第二大癌症死亡原因（仅次于肺癌）。2009年CRC的最新估计统计数据为：22 000例新病例和9 100例死亡。2009年加拿大估计的结直肠癌死亡人数为9100人（加拿大癌症协会）。因此，预防癌症，特别是结肠癌是非常重要的。利用益生菌进行癌症化学预防是一种抑制、延缓或逆转人类癌变的积极预防策略。一些研究提出，来自益生菌的微生物细胞壁成分（如细菌肽聚糖）可能是预防癌症的原因。然而，目前还没有研究证实这一假设，并阐明它们在癌症预防中的机制。通过对结肠癌细胞株的体外抗增殖试验，发现Bio-K+®菌株与5-氟尿嘧啶对结肠癌细胞株的凋亡有协同作用。在另一项体内预防被致癌物处理的大鼠异常隐窝灶（ACF）形成的研究中，Bio-K+®发酵乳被证明能够显著减少ACF（大鼠肠道癌前病变，与结肠癌有关）的形成。根据我们最近的研究，我们假设在最佳剂量下BioK+®发酵乳在体内具有很强的活性，可以预防被致癌物治疗的大鼠异常隐窝灶（ACF）的形成。此外，益生菌菌株在牛奶发酵过程中产生的生物活性成分可能是减少大鼠ACF形成的主要成分。本研究的目的是：1)通过体内实验研究BioK+®发酵乳减少癌前病变的剂量效应；2)通过体内实验从BioK+®发酵乳中分离出生物活性化合物并评价其减少癌前病变的作用。

Colon cancer is one of the leading causes of morbidity and mortality, not only in Western industrialized countries but also in developed Asian countries. Currently, colorectal cancer (CRC) is the 2nd leading cause of cancer death in Canada (after lung cancer). The most recent estimated statistics for CRC for 2009 are: 22,000 new cases and 9,100 deaths. Estimated CRC deaths in Canada in 2009 are 9,100 (Canadian Cancer Society). Therefore, prevention of cancer in generally and colon cancer in specifically is very important. The use of probiotic bacteria in cancer chemoprevention is an active preventive strategy to inhibit, delay or reverse human carcinogenesis. Some studies have proposed that microbial cell wall components from probiotic bacteria (ex: bacterial peptidoglycans) could be responsible of cancer prevention. However, no study have been done to confirm this hypothesis and to elucidate their mechanisms in cancer prevention. In an in vitro anti-proliferative test against colon cancer cell line, it was found that there was a synergistic effect of Bio-K+® bacterial strains with 5-Fluorouracil in enhancing the apoptosis in a colon cancer cell line. In another research on in vivo prevention of aberrant crypt foci (ACF) formation in rats treated with a carcinogen, Bio-K+® fermented milk was demonstrated to be able to reduce significantly the formation of ACF (a precancerous lesion in rat intestine and related to colon cancer). Based on our recent research, we suppose that BioK+® fermented milk at an optimized dose will have a strong in vivo activity in prevention of aberrant crypt foci (ACF) formation in rats treated with a carcinogenic agent. It is also supposed that bioactive components produced by probiotic strains during milk fermentation to produce Bio-K+® products may be the main components in reduction of ACF formation in rats. The objectives of this work are 1) to investigate the dose-effects of BioK+® fermented milk in reducing precancerous lesions in in vivo test and 2) to fractionate bioactive compounds from BioK+® fermented milk and evaluate their effects in reducing precancerous lesions in in vivo test.