内分泌激素联合化疗在乳腺癌治疗中的作用及机制研究

In principle of breast cancer treatment, endocrinotherapy can not be concurrently used with chemotherapy, because cancer cells retardant in G0 phase by endocrinotherapy are no more sensitive to chemotherapy. Nevertheless, decrease in hormones during chemotherapy is similar to concurrently using endocrinotherapy and chemotherapy, which severely goes against the principle of breast cancer treatment, and is followed with poor chemotherapeutic efficacy. Decrease in hormones during chemotherapy causes cell cycle arrest and renders tumor cells insensitive to chemotherapy and addition of endocrine hormones to mimic the hormones and microenvironment changes during chemotherapy for patients with choriocarcinoma-curable with chemotherapy only, will rescue tumor cells from cell cycle arrest rendering them sensitive to chemotherapy.It has been found in some basic researches that some therapeautics concurrently combined with endocrine hormones can achieve better efficacy compared with chemotherapy only.This new combinative therapy of concurrently using endocrine hormones and chemotherapy is defined firstly by us as choriocarcinoma-mimic chemotherapy or neo-endocrinochemotherapy to distinguish the routine term of endocrinochemotherapy and is expected to be a novel approach to enhance chemotherapeutic efficay in clinic. In this study, firstly, we aim to discuss the bad effect of endocrine hormones decreasing during chemotherapy in breast cancer cells and animal models, which determines the necessity of concurrently using endocrine hormones and chemotherapy. In addition, the feasibility and mechanisms of enhancing the chemosensitivity of breast cancer by endocrine hormones will be studied through breast cancer cells and animal models.

因作用机制不同，乳腺癌内分泌治疗不宜和化疗同时联用，否则会降低化疗疗效。然而，乳腺癌患者化疗期间常出现多种激素水平降低，即客观上存在化疗期间伴随内分泌治疗的现象，已经违背乳腺癌化疗不宜与内分泌治疗同时应用这一原则，势必影响乳腺癌患者化疗疗效。化疗期间内分泌激素降低使部分肿瘤细胞处于生长抑制状态，对化疗不敏感，通过额外添加内分泌激素模仿绒毛膜细胞癌等化疗可治愈性肿瘤化疗时的高甲状腺功能或高内分泌激素状态，从而促使肿瘤细胞进入活跃增殖周期，提高化疗敏感性，由此产生了仿绒毛膜细胞癌化学治疗学和乳腺癌等恶性肿瘤全新的化学治疗方式假说-新内分泌化疗。此种全新的治疗方式，已经基础实验初步论证可行，深入开展此项研究可能在乳腺癌治疗中取得里程碑的意义。因此，为探讨该疗法临床应用的可行性，我们将进一步通过体内外实验研究化疗期间激素减低的弊端和内分泌激素联合化疗的疗效，并明确新内分泌化疗的相关分子机制。

化疗作为一种全身性治疗手段，除对增生活跃的肿瘤细胞具有显著杀伤作用以外，对代谢活跃的内分泌系统也具有显著抑制作用。垂体-甲状腺轴功能活跃，在新陈代谢调节、促进人体发育、增加蛋白合成等生理活动中均具有重要作用，此外，其还被认为与肿瘤发生发展相关。主流观点认为，甲状腺激素可以促进乳腺癌细胞增殖。因此，通过我们前期小样本量研究发现化疗可以抑制甲状腺功能后，我们在本研究中假设化疗期间导致的甲功降低将会影响乳腺癌细胞对化疗的敏感性。经过进一步临床调查，我们发现甲状腺激素在化疗期间明显降低，并随访了部分患者的预后。在乳腺癌细胞培养过程中添加甲状腺激素，可以增加乳腺癌对化疗药物的敏感性，并初步从蛋白层面探讨了甲状腺激素的增敏机制。因此，我们正式提出乳腺癌全新的化学治疗方式-新内分泌化疗。此种全新的治疗方式，已经基础实验初步论证可行，深入开展此项研究将在乳腺癌治疗中取得里程碑的意义。