Concentration-dependent radiosensitizing effect of docetaxel in esophageal squamous cell carcinoma cells

  • Authors:
    • Shohei Miyanaga
    • Itasu Ninomiya
    • Tomoya Tsukada
    • Koichi Okamoto
    • Shinichi Harada
    • Shinichi Nakanuma
    • Seisho Sakai
    • Isamu Makino
    • Jun Kinoshita
    • Hironori Hayashi
    • Keishi Nakamura
    • Katsunobu Oyama
    • Hisatoshi Nakagawara
    • Tomoharu Miyashita
    • Hidehiro Tajima
    • Hiroyuki Takamura
    • Sachio Fushida
    • Tetsuo Ohta
  • View Affiliations

  • Published online on: December 14, 2015     https://doi.org/10.3892/ijo.2015.3291
  • Pages: 517-524
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Taxanes, paclitaxel and docetaxel (DTX) are anticancer agents that exhibit cytotoxicity by inhibiting microtubule polymerization. They enhance the radiosensitivity of various cancers by blocking the cell cycle in the most radiosensitive G2/M phase. Recently, taxanes have been reported to have different mechanisms of action depending on dose intensity. However, the mechanism of the radio-enhancing effect of DTX in relation to the drug dose intensity is not clearly understood. In the present study, we experimentally investigated the radio-enhancing effects of various concentrations of DTX against esophageal squamous cell cancer (ESCC); KES cells were used for in vitro confirmation of the effective administration schedule for DTX in chemoradiotherapy involving ESCC. DTX enhanced radiation cell killing in a concentration-dependent manner in KES cells. High cytotoxic concentrations (>10 nM) of DTX strongly enhanced radiosensitivity. Low concentrations (<1 nM) of DTX that did not have a cytotoxic effect showed a radio-enhancing effect by inducing DNA double strand breaks and apoptosis after irradiation. Low and high concentrations of DTX induced radiosensitive G0/G1 and G2/M phase arrest, respectively in KES cells. Cells treated with high concentrations of DTX exhibited nuclear aggregation associated with apoptotic change. In contrast, cells treated with low concentrations of DTX displayed multi-nucleation or unequal division. In conclusion, enhancement of the radiosensitivity of ESCC cells by DTX was demonstrated, even using nanomolar concentrations that did not have a cytotoxic effect. DTX has different radio-enhancing mechanisms depending on its concentration. Therefore, weekly administration of DTX might effectively enhance radiation cytotoxicity in the treatment of ESCC.

References

1 

Castro C, Bosetti C, Malvezzi M, Bertuccio P, Levi F, Negri E, La Vecchia C and Lunet N: Patterns and trends in esophageal cancer mortality and incidence in Europe (1980–2011) and predictions to 2015. Ann Oncol. 25:283–290. 2014. View Article : Google Scholar

2 

Ohtsu A, Boku N, Muro K, Chin K, Muto M, Yoshida S, Satake M, Ishikura S, Ogino T, Miyata Y, et al: Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol. 17:2915–2921. 1999.PubMed/NCBI

3 

Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE and Forastiere AA: An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 21:92–98. 2003. View Article : Google Scholar

4 

Ishida K, Ando N, Yamamoto S, Ide H and Shinoda M: Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: A Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516). Jpn J Clin Oncol. 34:615–619. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L and Emami B: Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 326:1593–1598. 1992. View Article : Google Scholar : PubMed/NCBI

6 

Kaneko K, Ito H, Konishi K, Kurahashi T, Ito T, Katagiri A, Yamamoto T, Kitahara T, Mizutani Y, Ohtsu A, et al: Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus. Br J Cancer. 88:18–24. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Choy H: Taxanes in combined modality therapy for solid tumors. Crit Rev Oncol Hematol. 37:237–247. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Ngeow J, Lim WT, Leong SS, Ang MK, Toh CK, Gao F, Chowbay B and Tan EH: Docetaxel is effective in heavily pretreated patients with disseminated nasopharyngeal carcinoma. Ann Oncol. 22:718–722. 2011. View Article : Google Scholar

9 

Bang YJ, Kang WK, Kang YK, Kim HC, Jacques C, Zuber E, Daglish B, Boudraa Y, Kim WS, Heo DS, et al: Docetaxel 75 mg/m(2) is active and well tolerated in patients with metastatic or recurrent gastric cancer: A phase II trial. Jpn J Clin Oncol. 32:248–254. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Abbrederis K, Lorenzen S, von Weikersthal LF, Vehling-Kaiser U, Schuster T, Rothling N, Peschel C and Lordick F: Weekly docetaxel monotherapy for advanced gastric or esophagogastric junction cancer. Results of a phase II study in elderly patients or patients with impaired performance status. Crit Rev Oncol Hematol. 66:84–90. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Nuzzo F, Morabito A, Gravina A, Di Rella F, Landi G, Pacilio C, Labonia V, Rossi E, De Maio E, Piccirillo MC, et al: Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: Results of a single-centre randomized phase 3 trial. BMC Cancer. 11:752011. View Article : Google Scholar : PubMed/NCBI

12 

Gravis G, Bladou F, Salem N, Macquart-Moulin G, Serment G, Camerlo J, Genre D, Bardou VJ, Maraninchi D and Viens P: Weekly administration of docetaxel for symptomatic metastatic hormone-refractory prostate carcinoma. Cancer. 98:1627–1634. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Perng RP, Shih JF, Chen YM, Chou KC, Lee YC and Tsai CM: A phase II study of single-agent docetaxel chemotherapy for non-small cell lung cancer. Jpn J Clin Oncol. 30:429–434. 2000. View Article : Google Scholar

14 

Kawada K, Kitagawa K, Kamei S, Inada M, Mitsuma A, Sawaki M, Kikumori T, Fujimoto Y, Arima H, Imai T, et al: The feasibility study of docetaxel in patients with anaplastic thyroid cancer. Jpn J Clin Oncol. 40:596–599. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Muro K, Hamaguchi T, Ohtsu A, Boku N, Chin K, Hyodo I, Fujita H, Takiyama W and Ohtsu T: A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer. Ann Oncol. 15:955–959. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Hennequin C, Giocanti N and Favaudon V: Interaction of ionizing radiation with paclitaxel (Taxol) and docetaxel (Taxotere) in HeLa and SQ20B cells. Cancer Res. 56:1842–1850. 1996.PubMed/NCBI

17 

Balcer-Kubiczek EK, Attarpour M, Wang JZ and Regine WF: The effect of docetaxel (taxotere) on human gastric cancer cells exhibiting low-dose radiation hypersensitivity. Clin Med Oncol. 2:301–311. 2008.PubMed/NCBI

18 

Mason KA, Hunter NR, Milas M, Abbruzzese JL and Milas L: Docetaxel enhances tumor radioresponse in vivo. Clin Cancer Res. 3:2431–2438. 1997.

19 

Yoshida T, Tokashiki R, Itoh H, Nakamura K, Hiramatsu H, Tsukahara K, Shimizu S, Takada D, Okamoto I, Abe K, et al: A phase I–II study of bi-weekly docetaxel combined with radiation therapy for patients with cancer of the larynx/hypopharynx. Jpn J Clin Oncol. 37:641–646. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Li YQ, Shi AH, Li FH, Yu R and Zhu GY: Phase I study to determine MTD of docetaxel and cisplatin with concurrent radiation therapy for Stage III non-small cell lung cancer. Chin J Cancer Res. 23:129–133. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Kiura K, Ueoka H, Segawa Y, Tabata M, Kamei H, Takigawa N, Hiraki S, Watanabe Y, Bessho A, Eguchi K, et al; Okayama Lung Cancer Study Group. Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer. Br J Cancer. 89:795–802. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Tishler RB, Norris CM Jr, Colevas AD, Lamb CC, Karp D, Busse PM, Nixon A, Frankenthaler R, Lake-Willcutt B, Costello R, et al: A Phase I/II trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prognosis squamous cell carcinoma of the head and neck. Cancer. 95:1472–1481. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Fujii M, Tsukuda M, Satake B, Kubota A, Kida A, Kohno N, Okami K and Inuyama Y; Japan Cooperative Head and Neck Oncology Group (JCHNOG). Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck. Int J Clin Oncol. 9:107–112. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Tishler RB, Posner MR, Norris CM Jr, Mahadevan A, Sullivan C, Goguen L, Wirth LJ, Costello R, Case M, Stowell S, et al: Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys. 65:1036–1044. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Clark JI, Eisner RM, Hofmeister C, Norton J, Thomas S, Choudhury A, Petruzzelli G, Lathers D, Young MR, Lau A, et al: Phase I adjuvant radiation with docetaxel in high-risk head and neck cancer. Am J Clin Oncol. 32:396–400. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Fukada J, Shigematsu N, Takeda A, Ohashi T, Tomita T, Shiotani A, Kunieda E, Kawaguchi O, Fujii M and Kubo A: Weekly low-dose docetaxel-based chemoradiotherapy for locally advanced oropharyngeal or hypopharyngeal carcinoma: A retrospective, single-institution study. Int J Radiat Oncol Biol Phys. 76:417–424. 2010. View Article : Google Scholar

27 

Onishi H, Kuriyama K, Yamaguchi M, Komiyama T, Tanaka S, Araki T, Nishikawa K and Ishihara H: Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: A good local response but no good survival due to radiation pneumonitis. Lung Cancer. 40:79–84. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Brunsvig PF, Hatlevoll R, Berg R, Lauvvang G, Owre K, Wang M and Aamdal S: Weekly docetaxel with concurrent radiotherapy in locally advanced non-small cell lung cancer: A phase I/II study with 5 years' follow-up. Lung Cancer. 50:97–105. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Kunos CA, Sill MW, Buekers TE, Walker JL, Schilder JM, Yamada SD, Waggoner SE, Mohiuddin M and Fracasso PM: Low-dose abdominal radiation as a docetaxel chemosensitizer for recurrent epithelial ovarian cancer: A phase I study of the Gynecologic Oncology Group. Gynecol Oncol. 120:224–228. 2011. View Article : Google Scholar :

30 

Font A, Arellano A, Fernández-Llamazares J, Casas D, Boix J, Cardenal J, Margelí M, Manzano JL, Abad A and Rosell R: Weekly docetaxel with concomitant radiotherapy in patients with inoperable oesophageal cancer. Clin Transl Oncol. 9:177–182. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Makino I, Okamoto K, Kinoshita J, Hayashi H, Nakamura K, Oyama K, Nakagawara H, Fujita H, Tajima H, Takamura H, et al: A pilot study of chemoradiotherapy with weekly docetaxel for thoracic esophageal carcinoma with T4 and/or M1 lymph node metastasis. World J Oncol. 2:252–258. 2011.

32 

Kushida T, Nohara S, Yoshino K, Fujiwara D, Ouchi K, Amano T, Isayama F, Tomita N, Iwanuma Y, Sasai K, et al: Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis. Dis Esophagus. 27:368–373. 2014. View Article : Google Scholar

33 

Moos PJ and Fitzpatrick FA: Taxanes propagate apoptosis via two cell populations with distinctive cytological and molecular traits. Cell Growth Differ. 9:687–697. 1998.PubMed/NCBI

34 

Torres K and Horwitz SB: Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res. 58:3620–3626. 1998.PubMed/NCBI

35 

Hernández-Vargas H, Palacios J and Moreno-Bueno G: Telling cells how to die: Docetaxel therapy in cancer cell lines. Cell Cycle. 6:780–783. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Zhang D, Yang R, Wang S and Dong Z: Paclitaxel: New uses for an old drug. Drug Des Devel Ther. 8:279–284. 2014.PubMed/NCBI

37 

Chaffey JT and Hellman S: Differing responses to radiation of murine bone marrow stem cells in relation to the cell cycle. Cancer Res. 31:1613–1615. 1971.PubMed/NCBI

38 

Parshad R, Gantt R, Sanford KK and Jones GM: Chromosomal radiosensitivity of human tumor cells during the G2 cell cycle period. Cancer Res. 44:5577–5582. 1984.PubMed/NCBI

39 

Paoletti A, Giocanti N, Favaudon V and Bornens M: Pulse treatment of interphasic HeLa cells with nanomolar doses of docetaxel affects centrosome organization and leads to catastrophic exit of mitosis. J Cell Sci. 110:2403–2415. 1997.PubMed/NCBI

40 

Morse DL, Gray H, Payne CM and Gillies RJ: Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells. Mol Cancer Ther. 4:1495–1504. 2005. View Article : Google Scholar : PubMed/NCBI

41 

Pradier O, Rave-Fränk M, Lehmann J, Lücke E, Boghun O, Hess CF and Schmidberger H: Effects of docetaxel in combination with radiation on human head and neck cancer cells (ZMK-1) and cervical squamous cell carcinoma cells (CaSki). Int J Cancer. 91:840–845. 2001. View Article : Google Scholar : PubMed/NCBI

42 

Clarke SJ and Rivory LP: Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet. 36:99–114. 1999. View Article : Google Scholar : PubMed/NCBI

43 

Bruno R and Sanderink GJ: Pharmacokinetics and metabolism of Taxotere (docetaxel). Cancer Surv. 17:305–313. 1993.PubMed/NCBI

44 

Brunsvig PF, Andersen A, Aamdal S, Kristensen V and Olsen H: Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy. BMC Cancer. 7:1972007. View Article : Google Scholar : PubMed/NCBI

45 

Milas L, Hunter NR, Mason KA, Kurdoglu B and Peters LJ: Enhancement of tumor radioresponse of a murine mammary carcinoma by paclitaxel. Cancer Res. 54:3506–3510. 1994.PubMed/NCBI

46 

Milas L, Hunter NR, Mason KA, Milross CG, Saito Y and Peters LJ: Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel. Cancer Res. 55:3564–3568. 1995.PubMed/NCBI

47 

McIlwrath AJ, Vasey PA, Ross GM and Brown R: Cell cycle arrests and radiosensitivity of human tumor cell lines: Dependence on wild-type p53 for radiosensitivity. Cancer Res. 54:3718–3722. 1994.PubMed/NCBI

Related Articles

Journal Cover

February 2016
Volume 48 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Miyanaga, S., Ninomiya, I., Tsukada, T., Okamoto, K., Harada, S., Nakanuma, S. ... Ohta, T. (2016). Concentration-dependent radiosensitizing effect of docetaxel in esophageal squamous cell carcinoma cells. International Journal of Oncology, 48, 517-524. https://doi.org/10.3892/ijo.2015.3291
MLA
Miyanaga, S., Ninomiya, I., Tsukada, T., Okamoto, K., Harada, S., Nakanuma, S., Sakai, S., Makino, I., Kinoshita, J., Hayashi, H., Nakamura, K., Oyama, K., Nakagawara, H., Miyashita, T., Tajima, H., Takamura, H., Fushida, S., Ohta, T."Concentration-dependent radiosensitizing effect of docetaxel in esophageal squamous cell carcinoma cells". International Journal of Oncology 48.2 (2016): 517-524.
Chicago
Miyanaga, S., Ninomiya, I., Tsukada, T., Okamoto, K., Harada, S., Nakanuma, S., Sakai, S., Makino, I., Kinoshita, J., Hayashi, H., Nakamura, K., Oyama, K., Nakagawara, H., Miyashita, T., Tajima, H., Takamura, H., Fushida, S., Ohta, T."Concentration-dependent radiosensitizing effect of docetaxel in esophageal squamous cell carcinoma cells". International Journal of Oncology 48, no. 2 (2016): 517-524. https://doi.org/10.3892/ijo.2015.3291