發明
中華民國
105120557
I 723030
二氫異丹蔘酮I於治療癌症之用途
長庚醫療財團法人
2021/04/01
癌症是世界上繼心冠狀血管疾病外第二名致死原因,僅僅在美國,每年就有超過五十萬人死於癌症。每年並有接近一百四十萬的新診斷病例。癌症細胞的特性即為不受控制的增生並且會侵犯周邊正常組織。並藉由淋巴或血液轉移至遠端器官或位置。雖然目前癌症治療手段,如化療、手術、放射線治療等,皆有長足進步,但都存在一定的副作用且有其侷限性,所以發展出更新的治療方法來對抗癌症轉移及抗藥性有其必要性。本純化物可以同時抑制多種癌症,包括前列腺癌、肺癌、大腸癌、乳癌、子宮內膜癌等,並對具有抗藥性的癌症,如對tamoxifen抗藥性的乳癌亦有抑制作用。同時本純化物亦可抑制相關癌症轉移,如前列腺癌、肺癌、大腸癌。就免疫系統而言,二氫異丹蔘酮會抑制癌細胞之誘發巨噬細胞聚集能力,同時二氫異丹蔘酮亦會抑制癌細胞在巨噬細胞培養液及兩者共生系統中的轉移能力,更進一步二氫異丹蔘酮會抑制巨噬細胞吸引癌細胞的能力。就機轉方面,我們發現二氫異丹蔘酮會抑制癌細胞及巨噬細胞中CCL2產生。同時兩者共生系統中的CCL2產生亦受到二氫異丹蔘酮抑制。由此可推論二氫異丹蔘酮會藉由抑制CCL2的產生,進而調控免疫系統抑制癌細胞轉移的作用。我們也發現二氫異丹蔘酮亦會調控skp2來控制癌細胞的轉移能力。更進一步,我們發現二氫異丹蔘酮在高濃度之下對巨噬細胞及裸鼠並無毒殺作用。本純化物是對治療癌症轉移及有抗藥性的癌症擁有發展前景的抗癌藥物。 Cancer is the second leading cause of death worldwide, after coronary artery disease. In the United States alone, cancer causes death of well over a half-million people each year, with some 1.4 million new cases diagnosed annually. Cancer cells are characterized by uncontrolled proliferation and the ability to invade surrounding normal tissue or distant sites by homological and/or lymphatic spread. Despite the advances made in cancer therapy, such as surgery, radiotherapy and chemotherapy, these therapeutic modalities are still associated with significant side effects. There is an unmet need for anti-cancer treatments with less side effects and/or for chemotherapy resistant or target therapy resistant cancers. The present invention provides methods for inhibiting or reducing cancer cells and chemotherapy resistant or target therapy resistant cancers (including prostate cancer, lung cancer, breast cancer, endometrial cancer, colorectal cancer and tamoxifen-resistant breast cancer) by administering to dihydroisotanshinone. Another aspect of the invention provides methods for reducing cancer metastasis (including prostate cancer, lung cancer and colorectal cancer), by administering an effective amount of dihydroisotanshinone. For immune system, dihydroisotanshinone may block the ability to promote cancer invasion in macrophage through CCL2 pathway. We also found dihydroisotanshinone may block the macrophage recruitment ability of cancer cells. Moreover, dihydroisotanshinone may block the prostate cancer cells invasion through inhibit skp2 pathway. We also found that DT hasn’t severe cytotoxicity in macrophage and nude mice. Our data suggest that dihydroisotanshinone can be developed as a potential therapeutic agent for cancer metastasis and chemotherapy resistant or target therapy resistant cancers.
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