Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
J Urol. 2013 Feb;189(2):711-8. doi: 10.1016/j.juro.2012.09.049. Epub 2012 Oct 8.
Evolutionarily early and late bacillus Calmette-Guérin substrains are genetically distinct, showing different antigenic determinants. While it was suggested that this may influence the immunostimulatory effects of bacillus Calmette-Guérin as a vaccine in the context of tuberculosis, to our knowledge the impact of these genetic differences on the antitumor activity of bacillus Calmette-Guérin remains unknown. We compared the direct antitumor capacity and the ability to trigger cytokine production of 8 evolutionarily early and late BCG substrains in urothelial bladder cancer cell lines.
The T24, J82 and RT4 bladder tumor cell lines were cultured with different doses of 3 evolutionarily early bacillus Calmette-Guérin substrains (Japan, Moreau and Russian) and 5 evolutionarily late strains (Connaught, Danish, Glaxo, Phipps and Tice). The inhibition of cell proliferation at different time points and the production of interleukin-6 and 8 in cell culture supernatants were measured.
For T24 and J82 cells Russian and Connaught induced the highest inhibition of cell proliferation and cytokine production, triggering values up to threefold higher than the other bacillus Calmette-Guérin strains. In contrast, Glaxo and Phipps (for T24 cells) and Glaxo and Tice (for J82 cells) were the least efficacious. For RT4 all bacillus Calmette-Guérin strains inhibited cell proliferation to a similar extent and induced low levels of only interleukin-8 except the Danish and Glaxo strains, which were less efficacious.
Russian and Connaught, which are evolutionarily early and late substrains, respectively, are the most efficacious bacillus Calmette-Guérin strains for inhibiting cell proliferation and inducing cytokine production. Glaxo is the least efficacious strain.
卡介苗的早期和晚期亚株在遗传上是不同的，表现出不同的抗原决定簇。虽然有人认为这可能影响卡介苗作为结核病疫苗的免疫刺激作用，但据我们所知，这些遗传差异对卡介苗的抗肿瘤活性的影响尚不清楚。我们比较了 8 株卡介苗早期和晚期亚株在膀胱癌细胞系中的直接抗肿瘤能力和触发细胞因子产生的能力。
用不同剂量的 3 株卡介苗早期亚株（日本、莫罗和俄罗斯）和 5 株卡介苗晚期亚株（康诺特、丹麦、葛兰素史克、菲普斯和泰西）培养 T24、J82 和 RT4 膀胱肿瘤细胞系。测量不同时间点细胞增殖的抑制率和细胞培养上清液中白细胞介素-6 和白细胞介素-8 的产生。
对于 T24 和 J82 细胞，俄罗斯和康诺特诱导的细胞增殖和细胞因子产生抑制作用最强，触发值比其他卡介苗菌株高 3 倍。相比之下，葛兰素史克和菲普斯（T24 细胞）和葛兰素史克和泰西（J82 细胞）的效果最差。对于 RT4，所有卡介苗菌株抑制细胞增殖的程度相似，除了丹麦和葛兰素史克株外，只诱导低水平的白细胞介素-8，而这两株的效果较差。
俄罗斯和康诺特分别是卡介苗的早期和晚期亚株，是抑制细胞增殖和诱导细胞因子产生最有效的卡介苗菌株。葛兰素史克株的效果最差。
