12月20日，据《每日科学》报道，ScienceDaily (Dec. 20, 2011)许多癌症疗法靶向于癌细胞外的特定蛋白质，但这些疗法是不完善的而且并不总是有效。既然能尽快让医生知道治疗对癌症的影响是有利的，Vanderbilt大学的研究人员正努力设计一些能迅速、准确且经济有效的测试方法用于评估治疗的反应。该研究小组已证明了一种新的方法，利用光学测试培养的癌细胞对一个特定抗癌药物的反应。
这项结果发表于Biomedical Optics Express 12期上。
某些特定的癌细胞呈现高于正常数值的蛋白，即一种称之为人类表皮生长因子受体2(HER2)。在正常细胞中，HER2有助于调解细胞的生长，但过度表达的HER2却标志着一种极具侵略性形式的乳腺癌。一些能结合和阻断生长因子受体的药物已被证明能够延长一些癌症患者的生命，但是约有30%的HER2过度表达的肿瘤对药物没有响应。能够在早期确定这些非响应肿瘤的测试方法，将帮助医生做出重要的治疗决策，以改善患者的预后。
为了设计这种测试方法，Vanderbilt团队利用了这样一个事实，就是一些癌细胞优先利用一种不同于正常细胞的代谢途径。研究人员通过使用各种频率的光照射细胞，使2种不同的代谢分子发出自然的荧光，从而可视化了2种不同代谢途径的相对使用情况。随后，他们计算了这2种水平的荧光的比率，称之为光光氧化还原率。他们发现，在测试的不同的细胞系中，HER2过表达的细胞有最高的光氧化还原率。他们还发现，当用一种HER2阻断药物作用HER2癌细胞时，光氧化还原率降低了。然而，在对这种药物有抗性的癌细胞中却没有观察到光氧化还原率的降低。这些发现为未来的体内研究奠定了基础，具有通过光学测量获知肿瘤对治疗的实时响应的潜力。（生物谷bioon.com）
doi:10.1364/BOE.3.000075
PMC:
PMID:
Optical imaging of metabolism in HER2 overexpressing breast cancer cells
Alex Walsh, Rebecca S. Cook, Brent Rexer, Carlos L. Arteaga, Melissa C. Skala
Abstract： The optical redox ratio (fluorescence intensity of NADH divided by that of FAD), was acquired for a panel of breast cancer cell lines to investigate how overexpression of human epidermal growth factor receptor 2 (HER2) affects tumor cell metabolism, and how tumor metabolism may be altered in response to clinically used HER2-targeted therapies. Confocal fluorescence microscopy was used to acquire NADH and FAD auto-fluorescent images. The optical redox ratio was highest in cells overexpressing HER2 and lowest in triple negative breast cancer (TNBC) cells, which lack HER2, progesterone receptor, and estrogen receptor (ER). The redox ratio in ER-positive/HER2-negative cells was higher than what was seen in TNBC cells, but lower than that in HER2 overexpressing cells. Importantly, inhibition of HER2 using trastuzumab significantly reduced the redox ratio in HER2 overexpressing cells. Furthermore, the combinatorial inhibition of HER2 and ER decreased the redox ratio in ER+/HER2+ breast cancer cells to a greater extent than inhibition of either receptor alone. Interestingly, trastuzumab had little impact upon the redox ratio in a cell line selected for acquired resistance to trastuzumab. Taken together, these data indicate that the optical redox ratio measures changes in tumor metabolism that reflect the oncogenic effects of HER2 activity within the cell, as well as the response of the cell to therapeutic inhibition of HER2. Therefore, optical redox imaging holds the promise of measuring response and resistance to receptor-targeted breast cancer therapies in real time, which could potentially impact clinical decisions and improve patient outcome.
