黄连与乌头对lewis肺癌细胞分化的作用比较

Comparative study of Coptidis Rhizoma and Aconiti Kusnezoffii Radix on cell differentiation in lewis lung cancer

黄连与乌头分别是寒凉药与温热药的代表,该研究的目的是观察黄连与乌头对lewis肺癌细胞的分化作用,比较寒凉药与温热药对肿瘤进展的影响。该研究制备黄连与乌头大鼠含药血清,体外培养lewis肺癌细胞,观察黄连与乌头含药血清对肿瘤细胞分化、增殖、黏附、琥珀酸脱氢酶活性及细胞间连接通讯的影响。建立小鼠lewis肺癌皮下移植及转移肿瘤模型,采用每日2次、连续4周给小鼠灌胃给药黄连与乌头水煎液治疗,检测小鼠体温、血氧饱和度、红细胞ATP酶活性、血流变、瘤内缺氧状态、毛细血管通透性及细胞间连接通讯,综合评价黄连与乌头对肿瘤进展的影响。结果发现乌头含药血清诱导lewis肺癌细胞分化,抑制细胞增殖和黏附,促进细胞琥珀酸脱氢酶活性及细胞间连接通讯。黄连含药血清虽也抑制细胞增殖,但无诱导细胞分化作用,且促进细胞黏附,抑制细胞琥珀酸脱氢酶活性及细胞间连接通讯。乌头水煎液能维持荷瘤小鼠体温、血氧饱和度、红细胞ATP酶活性和血流变,改善瘤内缺氧状态、毛细血管通透性及细胞间连接通讯,阻止肿瘤生长和转移。黄连水煎液虽也有一定阻止肿瘤生长作用,但降低小鼠体温、血氧饱和度、红细胞ATP酶活性、血流变和细胞间连接通讯,增加瘤内缺氧状态和毛细血管通透性,促进肿瘤转移。这些结果提示温热药可诱导肿瘤肿瘤细胞分化,阻止瘤毒内陷,比寒凉药更有利于肿瘤治疗。

Coptidis Rhizoma and Aconiti Kusnezoffii Radix represent hot Chinese medicine and cold Chinese medicine respectively. The purpose of this study is to observe the differentiation effect of Coptidis Rhizoma and Aconiti Kusnezoffii Radix on lewis lung cancer and compare effect of hot Chinese medicine and cold Chinese medicine on tumor progression. In this study,the rat serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix was prepared to treat lewis lung cancer cells in vitro,and effects of the serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix on cell differentiation,proliferation,adhesion,succinic dehydrogenase（ SDH） activity and gap-junction intercellular communication（ GJIC） were investigated. In vivo,the subcutaneous implant model and pulmonary metastasis model of lewis lung cancer were established. Tumor bearing mice were taken water decoction of coptis chinensis or aconite by intragastric administration bid for four weeks,and the influences of coptis chinensis and aconite on tumor progression were evaluated by body temperature,blood oxygen saturation,red cell ATPase,blood rheology,intratumor hypoxia,capillary permeability and GJIC. The results showed that the serum containing aconite could induce cell differentiation,inhibit cell proliferation and migration,promote SDH activity and GJIC in lewis lung cancer cells. The serum containing Coptidis Rhizoma increased cell adhesion and decreased SDH activity and GJIC without cell differentiation although it also suppressed cell proliferation. Aconiti Kusnezoffii Radix water decoction could keep body temperature,blood oxygen saturation,red cell ATPase and blood rheology,and improve intratumor hypoxia,capillary permeability and GJIC in tumor bearing mice,which led to slower tumor growth and less metastasis. Coptidis Rhizoma water decoction decreased body temperature,blood oxygen saturation,red cell ATPase,blood rheology and GJIC,and promoted intratumor hypoxia and capillary permeability,which resulted to more tumor metastasis although it also prevented tumor growth. These results suggested that the hot Chinese medicine could induce tumor cell differentiation and prevent tumor poison invagination,which is better for tumor treatment than cold Chinese medicine.