新型乳源性多肽ATPDM抗乳腺癌侵袭转移的作用与机制研究

The decreasing risk of incidence and metastasis of breast cancer has been confirmed with breastfeeding, however, The mechanism is unknown. ATPDM was a peptide identified by mass spectrometry, the aboudance of which was relatively high in colostrums, and it could inhibit cell invasion and migration, with no study between ATPDM and breast cancer. Software forecasted that PKM2 was the target of ATPDM. Research indicates that PKM2 affects the growth, invasion and metastasis of breast cancer by regulating metabolism. Preliminary experiment found that ATPDM and PKM2 had intracellular localization and affected Key molecular expression of its downstream, Prompting that ATPDM could combine with PKM2 and inhibit its expression, this may be the mechanism of inhibititing the invasion and metastasis of breast cancer. Study apply cell experiments and animal model to systemly evaluate the effect of ATPDM in the invasion and metastasis of breast cancer. Meaningwhile, taking the PKM2 as the point of the mechanism to reveal the action of ATPDM on the cell metabolism, invasion and migration; system evaluation the scientific hypothesis that ATPDM combined with PKM2, inhibited its expression,thus inhibiting the invasion and metastasis of breast cancer. From the perspectives of relationship between milk and tumor, our study will reveal the unknown function and mechanism of the peptide in the prevention and treatment of breast cancer, providing more basis to encourage breastfeeding . if Study obtain success, it will open up a new horizon for the prevention and treatment of breast cancer, which has revolutionary innovation .

母乳喂养可降低乳腺癌发病与转移风险，而机制未明。ATPDM是我们应用质谱技术筛选发现、在初乳中丰度较高、可抑制乳腺癌细胞侵袭转移的多肽，其与乳腺癌关系未见报道。软件预测PKM2为ATPDM靶基因，文献显示PKM2通过调节代谢而影响乳腺癌的生长、侵袭和转移。预实验发现，ATPDM与PKM2存在胞内共定位、并影响其下游关键分子表达，提示ATPDM通过与PKM2结合而抑制其表达，可能是抑制乳腺癌侵袭转移的机制。本研究拟通过体外与在体实验，全面评估ATPDM对乳腺癌侵袭转移的影响；同时以PKM2为切入点，揭示其影响乳腺癌细胞代谢与侵袭迁移的机制；从而系统评估“ATPDM通过与PKM2结合、抑制其表达，从而抑制乳腺癌侵袭转移能力”的科学假说。本课题从母乳与肿瘤关系视角，揭示多肽在防治乳腺癌中的未知功能和机制，为鼓励母乳喂养提供更多的依据。研究若获成功，将为预防和治疗乳腺癌开拓新视野，具有源头创新性。

癌细胞的侵袭转移是造成乳腺癌死亡率居高不下的主要原因之一。剖析其侵袭转移机制，寻找治疗新靶点、开发新药物，一直是乳腺癌防治的重中之重。母乳中含有的多肽，基于其分子量小、低毒、特异靶向等优点，已成为近年来肿瘤防治研究的热点之一，ATPDM是我们应用质谱技术筛选发现、在初乳中丰度较高、可抑制乳腺癌细胞侵袭转移的多肽。我们的研究发现，①不同浓度的ATPDM （0 μM 、10 μM、20 μM、50μM、100 μM）可以抑制乳腺癌细胞的增殖，迁移和侵袭能力；②不同浓度的ATPDM可以促进肿瘤细胞发生G1期阻滞；③不同浓度的ATPDM可以促进肿瘤细胞发生凋亡；④ 揭示了以PKM2为切入点，影响乳腺癌细胞代谢与侵袭迁移的机制。本课题从母乳与肿瘤关系视角，揭示多肽在防治乳腺癌中的未知功能和机制，为鼓励母乳喂养提供更多的依据。