Paclitaxel, from the bark and needles of Taxus brevifolia, is a tricyclic diterpenoid compound. Paclitaxel can promote the assembly of tubulin into microtubules and prevent the dissociation of microtubules, blocking cell cycle progression, preventing mitosis, and inhibiting the growth of cancer cells.[1]
In vitro, paclitaxel significantly inhibited the proliferation of ATC cells in a dose-dependent manner; the IC50 value ranged from 1.99 to 9.97 nM.[6] Encapsulating paclitaxel into nano-drug carriers, the water-solubility, selective delivery to cancers, tissue toxicity, controlled release and pharmacokinetic property of paclitaxel are improved, can improve its toxicity to human, keep or enhance its activity and improve its pharmacokinetic property.[2] In vitro, in a short time, exposures to paclitaxel induced the phosphorylation and degradation of IkappaB-alpha, which in turn caused the activation of NF-kappaB in both human breast cancer BCap37 and human epidermoid carcinoma KB cells. [3] In addition, Paclitaxel can increase its cytotoxic effect by the loading of Paclitaxel to autologous prostate cancer cell-derived EVs.[5]
In vivo experiment it shown that treatment with 1 mg/kg and 20 mg/kg paclitaxel, the light-colored spotted metastases were dramatically increased in livers from the low-dose paclitaxel-treated mice and the metastasis was substantially reduced in the high-dose paclitaxel group.[4] In vivo, the growth of C643 cell-derived xenograft tumors in the lenvatinib-treated (5 mg/kg; p.o.) and paclitaxel-treated (5 mg/kg;i.p.) groups was slower than that in control group.[6]
References:
[1]Zhu L, Chen L. Progress in research on paclitaxel and tumor immunotherapy. Cell Mol Biol Lett. 2019 Jun 13;24:40.
[2]Chen S, et al. Recent Development of Copolymeric Nano-Drug Delivery System for Paclitaxel. Anticancer Agents Med Chem. 2020;20(18):2169-2189.?
[3]Dziadyk JM, et al. Paclitaxel-induced apoptosis may occur without a prior G2/M-phase arrest. Anticancer Res. 2004 Jan-Feb;24(1):27-36.?
[4]Li Q, et al. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model. FEBS J. 2016 Aug;283(15):2836-52.
[5]Saari H, et al. Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. J Control Release. 2015 Dec 28;220(Pt B):727-37.?
[6]Jing C, et al. Lenvatinib enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer. Am J Cancer Res. 2017 Apr 1;7(4):903-912.
紫杉醇是从短叶红豆杉的树皮和针叶中提取出来的三环二萜化合物。它可以促进微管蛋白聚集成微管，并防止微管解离，从而阻碍细胞周期进展、预防有丝分裂并抑制癌细胞生长。[1]
在体外实验中，紫杉醇以剂量依赖的方式显著抑制了ATC细胞的增殖；IC50值范围为1.99至9.97纳摩尔。将紫杉醇封装到纳米药物载体中可以提高其水溶性、选择性地传递给癌细胞、组织毒性、控制释放和药代动力学特性，从而改善其对人体的毒性，保持或增强其活性并改善其药代动力学特性。在 vitro 实验中，在短时间内接触紫杉醇可诱导 IkappaB-alpha 的磷酸化和降解，进而导致 NF-kappaB 在人乳腺癌BCap37和人表皮样癌KB细胞中被激活。此外，通过将紫杉醇加载到自体前列腺癌细胞衍生的EVs上可以增强其细胞毒作用。
在体内实验中，使用1毫克/千克和20毫克/千克紫杉醇治疗后，低剂量紫杉醇处理的小鼠肝脏中浅色斑点转移显著增加，而高剂量紫杉醇组的转移明显减少。在体内，C643细胞来源的异种移植瘤在接受5毫克/千克口服利妥昔单抗和5毫克/千克腹腔注射紫杉醇处理组中生长速度较缓慢，比对照组要慢。