Mourad W A, Bruner J M, Vallieres E, McName C, Alabdulwahed S, Scott K, Oldring D J
Department of Pathology, University of Alberta, Edmonton, Canada.
In Vivo. 1996 May-Jun;10(3):329-33.
In vitro studies have suggested that vitamin A lowers invasive potential of squamous cell carcinoma. Epidemiological data have also indicated that high dose vitamin A may improve survival in patients with previously resected lung carcinoma. To our knowledge, no studies have attempted to test the in vivo effect of vitamin A on the morphology and growth rate of lung and head and neck cancer. Freshly resected tumor cell suspensions were obtained by ex vivo fine needle aspiration and injected subcutaneously in duplicate in athymic male nude mice. Two to six weeks post-engraftment tests and controls were separated for each xenograft. Mice with test xenografts were given water soluble vitamin A (Aquasol ATM, Astra pharmaceutical, Westborough, MA, U.S.A) at a dose of 10,000 U/Kg/day intraperitoneally for 6 to 10 weeks (median 8 weeks). One to two hours prior to sacrifice bromodexouridine (BrdU) was injected intraperitoneally to assess the S-phase fraction in both test and control xenografts. Blood vitamin A levels in test and control animals were measured after sacrifice using high performance liquid chromatography (HPLC). Sections of test and control xenografts were routinely stained to assess morphologic differentiation and mitotic counts. Unstained sections of xenografts were immunostained by the antibody to BrdU to test for BrdU labeling index (BLI) reflecting S-phase fraction (SPF) and also by the MIB-1 antibody to assess proliferative activity. Eighteen tumors were studied. These included 9 squamous cell carcinomas of the lung, 5 squamous cell carcinomas of the head and neck, and 4 adenocarcinomas of the lung. Blood levels of vitamin A in test animals were 7 to 23 times those of the control animals (median 13 times). Neovascularization of the xenografts was seen in all cases. The morphology and mitotic activity of the test and control xenografts showed no significant difference. SPF and proliferative activity measured by BrdU and MIB-1 immunolabelling respectively showed no significant difference between test and control xenografts. Our study suggests that there is no significant in vivo effect of high dose vitamin A on the morphology and growth rate of xenografted non small cell carcinoma of the lung or squamous cell carcinoma of the head and neck.
体外研究表明，维生素A可降低鳞状细胞癌的侵袭潜能。流行病学数据也表明，高剂量维生素A可能会改善既往接受过肺癌切除术患者的生存率。据我们所知，尚无研究试图检测维生素A对肺癌及头颈部癌的形态和生长速率的体内作用。通过体外细针穿刺获取新鲜切除的肿瘤细胞悬液，并一式两份皮下注射到无胸腺雄性裸鼠体内。移植后2至6周，将每个异种移植的试验组和对照组分开。给带有试验性异种移植瘤的小鼠腹腔注射剂量为10,000 U/Kg/天的水溶性维生素A（美国马萨诸塞州韦斯特伯勒市阿斯特拉制药公司的Aquasol ATM），持续6至10周（中位数为8周）。在处死前1至2小时，腹腔注射溴脱氧尿苷（BrdU），以评估试验组和对照组异种移植瘤中的S期分数。处死动物后，使用高效液相色谱法（HPLC）测量试验组和对照组动物的血液维生素A水平。对试验组和对照组异种移植瘤的切片进行常规染色，以评估形态学分化和有丝分裂计数。对异种移植瘤的未染色切片用抗BrdU抗体进行免疫染色，以检测反映S期分数（SPF）的BrdU标记指数（BLI），还用MIB-1抗体进行免疫染色以评估增殖活性。共研究了18个肿瘤。其中包括9例肺鳞状细胞癌、5例头颈部鳞状细胞癌和4例肺腺癌。试验组动物的血液维生素A水平是对照组动物的7至23倍（中位数为13倍）。在所有病例中均可见异种移植瘤的新生血管形成。试验组和对照组异种移植瘤的形态和有丝分裂活性无显著差异。分别通过BrdU和MIB-1免疫标记测量的SPF和增殖活性在试验组和对照组异种移植瘤之间无显著差异。我们的研究表明，高剂量维生素A对异种移植的非小细胞肺癌或头颈部鳞状细胞癌的形态和生长速率无显著体内作用。
