Oyenihi Omolola R, Krygsman Annadie, Verhoog Nicolette, de Beer Dalene, Saayman Michael J, Mouton Thys M, Louw Ann
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
Front Pharmacol. 2018 Jun 20;9:650. doi: 10.3389/fphar.2018.00650. eCollection 2018.
Breast cancer (BC) is the leading cause of cancer-related deaths in women. Chemoprevention of BC by using plant extracts is gaining attention. SM6Met, a well-characterized extract of with reported selective estrogen receptor subtype activity, has shown tumor suppressive effects in a chemically induced BC model in rats, which is known to be estrogen responsive. However, there is no information on the estrogen sensitivity of the relatively new orthotopic model of LA7 cell-induced mammary tumors. In the present study, the potential chemopreventative and side-effect profile of SM6Met on LA7 cell-induced tumor growth was evaluated, as was the effects of 17β-estradiol and standard-of-care (SOC) endocrine therapies, such as tamoxifen (TAM), letrozole (LET), and fulvestrant (FUL). Tumor growth was observed in the tumor-vehicle control group until day 10 post tumor induction, which declined afterward on days 12-14. SM6Met suppressed tumor growth to the same extent as TAM, while LET, but not FUL, also showed substantial anti-tumor effects. Short-term 17β-estradiol treatment reduced tumor volume on days prior to day 10, whereas tumor promoting effects were observed during long-term treatment, which was especially evident at later time points. Marked elevation in serum markers of liver injury, which was further supported by histological evaluation, was observed in the vehicle-treated tumor control, TAM, LET, and long-term 17β-estradiol treatment groups. Alterations in the lipid profiles were also observed in the 17β-estradiol treatment groups. In contrast, SM6Met did not augment the increase in serum levels of liver injury biomarkers caused by tumor induction and no effect was observed on lipid profiles. In summary, the results from the current study demonstrate the chemopreventative effect of SM6Met on mammary tumor growth, which was comparable to that of TAM, without eliciting the negative side-effects observed with this SOC endocrine therapy. Furthermore, the results of this study also showed some responsiveness of LA7-induced tumors to estrogen and SOC endocrine therapies. Thus, this model may be useful in evaluating potential endocrine therapies for hormone responsive BC.
乳腺癌（BC）是女性癌症相关死亡的主要原因。利用植物提取物对BC进行化学预防正受到关注。SM6Met是一种特征明确的提取物，具有报道的选择性雌激素受体亚型活性，在化学诱导的大鼠BC模型中显示出肿瘤抑制作用，该模型已知对雌激素有反应。然而，关于相对较新的LA7细胞诱导乳腺肿瘤原位模型的雌激素敏感性尚无信息。在本研究中，评估了SM6Met对LA7细胞诱导的肿瘤生长的潜在化学预防作用和副作用情况，以及17β-雌二醇和标准护理（SOC）内分泌疗法（如他莫昔芬（TAM）、来曲唑（LET）和氟维司群（FUL））的效果。在肿瘤载体对照组中，直到肿瘤诱导后第10天观察到肿瘤生长，之后在第12 - 14天下降。SM6Met抑制肿瘤生长的程度与TAM相同，而LET（但不是FUL）也显示出显著的抗肿瘤作用。短期17β-雌二醇治疗在第10天之前减小了肿瘤体积，而在长期治疗期间观察到肿瘤促进作用，在后期时间点尤其明显。在载体处理的肿瘤对照组、TAM、LET和长期17β-雌二醇治疗组中观察到肝损伤血清标志物显著升高，组织学评估进一步证实了这一点。在17β-雌二醇治疗组中也观察到脂质谱的改变。相比之下，SM6Met没有增加肿瘤诱导引起的肝损伤生物标志物血清水平的升高，并且对脂质谱没有影响。总之，本研究结果证明了SM6Met对乳腺肿瘤生长的化学预防作用，其与TAM相当，且不会引发这种SOC内分泌疗法所观察到的负面副作用。此外，本研究结果还显示LA7诱导的肿瘤对雌激素和SOC内分泌疗法有一定反应性。因此，该模型可能有助于评估激素反应性BC的潜在内分泌疗法。
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