To determine which caspases are involved in apoptosis induced by taxol, caspase-3 inhibitor (DEVD-CHO), caspase-6 inhibitor (Z-VEID-FMK), caspase-8 inhibitor (Z-IETD-FMK or IETD-CHO), caspase-9 inhibitors (Z-LEHD-FMK or LEHD-CHO), and caspase-10 inhibitor (Z-AEVD-FMK) are used. These caspase inhibitors are dissolved in dimethyl sulfoxide (Me₂SO); the final concentration of Me₂SO is 0.1%. Cells (5×10⁵) are preincubated in the presence or absence of 100 μM each of these inhibitors for 3 h at 37°C then treated with or without 0.1, 0.5, and 1 μM Paclitaxel for 48 h and processed for annexin V binding assay.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

1×10⁴ cells are plated in 100 μL of the growth medium in the presence or absence of increasing concentrations (0.1-1 μM) of taxol in 96-well plates and cultured at 37°C in 5% CO₂ for 12-48 h. The cells are then incubated with 25 μL of MTT (5 mg/mL) at 37°C for 4 h. After dissolving the crystals with 0.04 N HCl in isopropanol, the plates are read in a microplate reader at 570 nm. The concentration of drug that inhibits cell survival by 50% (IC₅₀) is determined from cell survival plots.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Adult (250-320 g) male Sprague-Dawley rats are used for all experiments. Rats are housed two per cage in a temperature and humidity controlled, on a 12 h:12 h light:dark schedule with food and water available ad libitum. One week following the DiI injection, rats are anesthetized with isofluorane and injected into the tail vein with 2 mg/kg paclitaxel or its vehicle (1:1:23, cremophor EL:ethanol:0.9% saline). The tail vein injection is repeated three more times every other day for a total of four injections.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Park SJ, et al. Taxol induces caspase-10-dependent apoptosis. J Biol Chem. 2004 Dec 3;279(49):51057-67. Epub 2004 Sep 27.

  [2]. Pan Z, et al. Paclitaxel attenuates Bcl-2 resistance to apoptosis in breast cancer cells through an endoplasmic reticulum-mediated calciumrelease in a dosage dependent manner. Biochem Biophys Res Commun. 2013 Feb 13. pii: S0006-291X(13)00259-3.

  [3]. Cadamuro M, et al. Low dose paclitaxel reduces S100A4 nuclear import to inhibit invasion and hematogenous metastasis of cholangiocarcinoma. Cancer Res. 2016 Jun 21.

  [4]. Li Q, et al. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model. FEBS J. 2016 Jun 16.

  [5]. Yilmaz E, et al. Sensory neuron subpopulation-specific dysregulation of intracellular calcium in a rat model of chemotherapy-induced peripheral neuropathy. Neuroscience. 2015 Aug 6;300:210-8.

  [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.

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