超音波熱治療結合Metformin與免疫刺激劑增強全身性抗腫瘤免疫反應

Abstract

低強度脈衝波的超音波治療是一項具有前瞻性的研究，通過其所產生的熱效應與非熱效應的機制可達到抑制腫瘤生長的效果。脈衝式超音波在惡性腫瘤組織上加熱可直接殺死腫瘤細胞。然而，在原發性腫瘤消除後仍可能發生腫瘤復發與轉移的情形。為了獲得更良好的預後，我們將其他兩種藥物，即二甲雙胍和OK-432與脈衝式超音波治療做結合。根據先前的研究，二甲雙胍在調節免疫系統上有作用;另外，OK-432免疫刺激劑可以活化並且強化免疫系統。儘管如此，結合三者治療腫瘤的療效尚未被研究。在這項研究中，目的是探究由脈衝式超音波與二甲雙胍和OK-432所結合的治療效果。我們實驗結果顯示，三聯療法(脈衝式超音波結合二甲雙胍及OK-432治療組)相較於其他組別的結合療法，確實顯著地抑制腫瘤生長，這表示三聯療法具有顯著抗腫瘤效果。治療期後可能產生的腫瘤復發及轉移機率均受到顯著地抑制。熱療法與免疫療法的結合可能引發多方面的抗癌反應。我們的實驗結果呈現出，此方式的結合療法具有相當的潛力應用在腫瘤治療。

Low intensity pulsed-wave ultrasound is a prospective way to inhibit tumor growth with its thermal and non-thermal effects. Tumor cells can be killed by heating directly on malignant tumor tissue. However, tumor recurrence and metastasis still may occur after the primary tumor is eliminated. Trying to obtain a better prognosis, we performed pulsed-wave ultrasound with other two medical treatments: Metformin and OK-432. Based on previous studies, Metformin performs a vital role in mediating immune response. Injection of OK-432, an immunostimulant, causes activation of robust immune system. Even though with perspective advantages, the efficacy of this combined therapy has not been reported. In this study, we aimed to examine the effect of mild heating generated by pulsed-wave ultrasound in combination with Metformin and OK-432. Our results showed that tumor growth was significantly suppressed by triple therapy in comparison with other treatment groups. This indicates that antitumor response has increased effectively. Meanwhile, the risk of both recurrence and metastasis were inhibited remarkably. Combining thermal therapy with immunotherapy strategies may elicit multifaceted anticancer immunity. Our experimental results displayed that the combination of ultrasound hyperthermia with Metformin and immunostimulant might be an alternative and promising strategy against recurrence and metastasis on colorectal carcinoma.